Surface-enhanced Raman spectroscopy and microfluidic platforms: challenges, solutions and potential applications.

The exhaustive body of literature published in the last four years on the development and application of systems based on surface-enhanced Raman spectroscopy (SERS) combined with microfluidic devices demonstrates that this research field is a current hot topic. This synergy, also referred to as lab-on-a-chip SERS (LoC-SERS) or nano/micro-optofluidics SERS, has opened the door for new opportunities where both techniques can profit. On the one hand, SERS measurements are considerably improved because the processes previously performed on a large scale in the laboratory and prone to human error can now be carried out in nanoliter volumes in an automatic and reproducible manner; on the other hand, microfluidic platforms need detection methods able to sense in small volumes and therefore, SERS is ideal for this task. The present review not only aims to provide the reader an overview of the recent developments and advancements in this field, but it also addresses the key aspects of fundamental SERS theory that influence the interpretation of SERS spectra, as well as the challenges brought about by the experimental conditions and chemometric data analysis.

[Sex/Gender-Responsive Health Research: New Funding Guidelines of the USA National Institutes of Health Can Bring a New Impetus to Germany]. / Geschlechtergerechte Gesundheitsforschung - Aktuelle Vorgaben der National Institutes of Health in den USA können neuen Schwung auch nach Deutschland bringen - Diskussionsbeitrag.

In June 2015, the National Institutes of Health (NIH) of the USA published a new funding guideline entitled "Consideration of Sex as a Biological Variable in NIH-funded Research". This guideline is part of the NIH policy to enhance quality and generalizability of health research. Its core element is the classification of sex as a key element of rigorous study designs. The requirement is that sex be defined as a biological variable, and taking the potentially relevant sex/gender related anatomical and physiological characteristics into account. In Germany, the "Guidelines and recommendations to assure good epidemiological practice" (GEP) of 1998 specify that the study design and research methods are to be designed so that sex/gender-specific aspects of the research question can be adequately detected. Mostly health research is restricted to the categorization of the study population into men and women and to the consideration of the sex/gender variable (man*woman) in the analyses. Research in accordance with the NIH guideline as well as with the German GEP needs to investigate differences and similarities between men and women, and also to look for factors that explain in what way being a man or a woman poses a risk or is protective against the development of diseases. This scientific basis is essential for the development and implementation of sex/gender equitable prevention, health promotion and health care, which in turn enables statutory health insurances to take sex/gender differences into account regarding the medical services they provide. The latter is a consequence of the current legal position in Germany, which is based on the Prevention law that was passed in 2015. In addition to the categorical sex/gender variable (man*woman), there is therefore the need to analytically differentiate between the dimensions sex (the biological factors) and gender (the socio-cultural ascriptions) as well as their interaction. For conceptual clarity, this paper proposes that the terms sex and/or gender be used only where the biological and/or socio-cultural aspects of being a man or a woman are explicitly taken into account. For the common sex/gender variable man*woman (based on self-reports, register data etc.) the term Survey sex (German: Erhebungsgeschlecht) can be used. Further, the establishment of a Federal Institute "Geschlecht und Gesundheit - Sex/Gender and Health" is recommended.

[Sex/Gender-sensitive Research - A Survey of Epidemiologists in Germany]. / Geschlechtersensible Forschung - ein Survey unter Epidemiologinnen und Epidemiologen in Deutschland.

BACKGROUND AND AIMS: Epidemiology is the basic science of Public Health and has to provide high-quality scientific evidence for disease prevention and health care. Sex/Gender, as social and biological structure categories of population, play a central role in the analysis of epidemiological data. Whether and how epidemiologists incorporate sex/gender aspects in their research, their attitudes, needs and requirements they have in this context have hardly been investigated. These questions were addressed in a survey of epidemiologists in Germany. METHODS: With the support of the respective scientific societies, an online survey was conducted of German epidemiologists, and the data subjected to descriptive analysis. RESULTS: Approximately 64% of the 276 participants (response rate 25%) were female and 75% worked in the academic field. 70% reported having had experience in sex/gender-sensitive research and 83% expressed future interest in this topic. Issues mentioned as important were interaction of gender aspects and other factors of social inequality as well as the inclusion of sex and gender in all phases of the research process. Women and younger participants reported more experience and more needs concerning sex/gender sensitive research. To facilitate further incorporation of sex/gender-sensitive research in epidemiology, special workshops/tutorials at the respective scientific societies' annual meetings and online information materials were rated as important. CONCLUSION: Due to the low response rate, a positive selection of participants cannot be ruled out. The results show that, while a large group of epidemiologists had experience and interest in gender-sensitive research, there are some with less interest. Possible starting points for the strengthening of sex/gender-sensitivity research include further training and involvement of scientific societies in the process.

[Reaching Target Groups--Shaping Accessibility. Results of a Survey Among Experts on Recommendations for Science and Practice]. / Zielgruppen erreichen--Zugangswege gestalten. Ergebnisse einer Befragung von Expertinnen und Experten zu Empfehlungen für Wissenschaft und Praxis.

In an online survey, in which 18 experts participated, recommendations for research and practice to improve access to target groups were discussed. The recommendations were developed within the context of the KNP project. For the implementation of the recommendations, not only is an increased cooperation between science and practice particularly important, but also materials and training as well as standardization of methods. Furthermore, financial resources, especially for conducting evaluation studies are needed.

[Prevention of Obesity and Promotion of Healthy Nutrition in Children by a Kindergarten-Based Intervention: An Evaluation Study]. / Übergewichtsprävention und Förderung gesunder Ernährung bei Kindern: Evaluation eines institutionellen Verpflegungskonzeptes.

This outcome evaluation study has investigated different diet concepts in day-care centres and their effects on health-related dietary behaviour of children and their families. No advantage of a certain approach to manage food and diet-related activities in day-care centres could be shown.

[Reaching Target Groups--Shaping Accessibility]. / Zielgruppen erreichen--Zugangswege gestalten.

This paper describes the public health discourse on the accessibility and access paths, theoretical approaches as well as factors influencing the utilisation of prevention and health promotion interventions, and requirements for their evaluation. Various projects funded by the German Federal Ministry of Education and Research address many aspects of accessibility and describe extensive experiences with access paths, approaches to information transfer, target group-driven supply chain design, etc. Recommendations for practice and research are given at the end of the article.

[How do Prevention Projects Reach their Target Groups? Results of a Survey with Prevention Projects]. / Wie erreichen Präventionsprojekte ihre Zielgruppen? Auswertung einer Befragung der im Rahmen des BMBF-Förderschwerpunkts Präventionsforschung geförderten Projekte.

AIM: The aim of this study was to assess methods used to access target groups in prevention projects funded within the prevention research framework by the German Federal Ministry of Education and Research. METHODS: A survey with prevention projects was conducted. Access strategies, communication channels, incentives, programme reach, and successful practical recruitment strategies were explored. RESULTS: 38 out of 60 projects took part in the survey. Most projects accessed their target group within structured settings (e. g., child day-care centers, schools, workplaces). Multiple communication channels and incentives were used, with written information and monetary incentives being used most frequently. Only few projects were able to report their programme reach adequately; programme reach was highest for programmes accessing the target groups in structured settings. The respondents viewed active recruitment via personal communication with the target group and key persons in the settings as the most successful strategy. CONCLUSION: The paper provides an overview on recruitment strategies used in current preven-tion projects. More systematic research on programme reach is necessary.

[Sex- and gender-sensitive research in epidemiology and medicine: how can this be achieved? Aims and first results of the network "Sex-/Gender-Sensitive Research in Epidemiology, Neurosciences and Genetics/Cancer Research"]. / Geschlechtersensible Forschung in Epidemiologie und Medizin: Wie kann das erreicht werden? : Ziele und erste Ergebnisse des Verbundes "Geschlechtersensible Forschung in Epidemiologie, Neurowissenschaften und Genetik/Tumorforschung".

BACKGROUND: It is considered general knowledge among physicians and epidemiologists that biological and social aspects associated with being male or female have a strong influence on health and disease. Integrating these aspects into research is necessary to counteract the problems--including ethical problems--resulting from a different evidence basis for men and women. From January 2011 to June 2014 the Federal Ministry of Education and Research supported the network "Sex-/Gender-Sensitive Research in Epidemiology, Neuroscience and Genetics/Cancer Research" with three subprojects, which aimed to promote gender-sensitive research practices. The concepts and results are presented in this article. METHODS: The subproject gathered data (literature analyses, questionnaires) and offered programs for young scientists. Experiences and results were collected and generalized, for instance, in the form of definitions of terms. RESULTS: 50 young scientists have taken part in the training program, identifying associations and barriers in sex-/gender-sensitive research. Among others, a working definition for "sex-/gender-sensitive research" was developed, as well as definitions for the terms "sex-specific" (for biological characteristics that are specific to men or women) and "sex-/gender-dependent" or "sex-/gender-associated" (for biological and social factors, for which the extent of occurrence differs between the sexes). PRELIMINARY ASSESSMENT: The concepts realized by the network are well suited to stimulate further development and discussions. The definition of terms is an important base for a productive and high-yielding interdisciplinary collaboration.

[Assertive community treatment in patients with severe obsessive-compulsive disorders]. / Aufsuchende gemeindepsychiatrische Behandlung bei Patienten mit schweren Zwangsstörungen.

For the use of psychosocial treatments for severe mental illness, there is a high evidence level. Obsessive-compulsive disorders are accompanied by severe disabilities in one third of the cases, however, there is little scientific research on the use of psychosocial therapies in patients with obsessive-compulsive disorders. In the following, the concept of an outreaching multi-professional treatment based on the assertive community treatment (ACT) method for severe compulsive illnesses is presented and discussed based on two case studies. There was an obvious reduction in clinically rated severity of obsessive-compulsive disorder symptoms, as measured by the Yale-Brown obsessive-compulsive scale (Y-BOCS), over the course of ACT. Comparison between pre- and post-treatment states demonstrated a reduction in the total Y-BOCS score after the treatment (case 1: total Y-BOCS score 37 versus 26; case 2: total Y-BOCS score 36 versus 16).

[Memorandum prevention research - research areas and methods]. / Memorandum zur Präventionsforschung - Themenfelder und Methoden (Langfassung).

From 2004 to 2012, the German Ministry of Education and Research (BMBF) established its first funding programme for the promotion of prevention research. 60 projects on primary prevention and health promotion and the meta-project entitled "Cooperation for Sustainable Prevention Research" (KNP) received BMBF grants under this programme during this period. The experience and knowledge gained and recommendations arising from the research funded under this programme are compiled in memorandum format. The "Memorandum on Prevention Research - Research Areas and Methods" highlights 5 research areas that are considered to be especially relevant from the perspective of the involved scientists and practice partners.The promotion of structural development and sustainability enhancement in disease prevention and health promotion are central areas that should branch out from existing nuclei of crystallization. Improving the health competence of the population and of specific subpopulations is another major area. Research in these areas should contribute to the development of theoretical concepts and to the empirical testing of these concepts. The transfer of knowledge for effective use of developed disease prevention and health promotion programmes and measures is still a scarcely researched area. Among other things, studies of the transfer of programmes from one context to another, analyses of the coop-eration between politics and science, and the continued theoretical and conceptual development of transfer research are needed. Long-term data on the effects of intervention studies are also needed for proper evaluation of sustainability. The latter dem-onstrates the importance of method development in disease prevention and health promotion research as an area that should receive separate funding and support. This research should include, in particular, studies of the efficacy of complex interventions, health economic analyses, and participative health research.

[Memorandum - research funding of prevention]. / Memorandum - Forschungsförderung Prävention.

The memorandum of the research funding of prevention has been devised within the framework of the Prevention Research Funding Programme of the Federal Ministry of Education and Research. It consists not only of the obtained findings of the research-practice co-operation but also of recommendations for the implementation of prospective, innovational, effective, practice-oriented and sustainable research. The respective knowledge has been acquired from quantitative surveys on the experiences of scientists and practice partners within the prevention research funding project as well as from extensive qualitative methods of structured group evaluation. A participatory co-operation between research and practice based on mutual respect, trust and recognition is seen as mandatory for the further development of both prevention and health promotion research. Research and practice partners are required to engage in an ab initio collaboration starting from the conception phase, whereby it is advisable to encourage and fortify the communication between research, practice and funding partners by systematic surveillance in form of a meta-project. In addition, the inclusion of the target population from the outset and on a collaborative basis is considered as beneficial in order to ensure the practical application of the research findings. Furthermore, innovatory research designs which are able to provide a framework for internal flexibility, continuous re-assessment and adjustment are fundamental for the implementation of practice-oriented research. Moreover, a dynamic co-operation between different groups of interest not only depends on sharing responsibility but also on sufficient funding for both research and practice, which is particularly important for the transfer and communication of the attained findings. With regard to the evaluation of both effectiveness and sustainability of interventions, a research funding project is required which makes long-term results possible through the utilization of regulated monitoring and guarantees quality and continuous effectiveness. Furthermore, in order to stimulate progress within the basic theories of prevention and health promotion, it is also essential for a funding project to focus on elementary concepts. Additionally, for the efficient and sustainable development of health within a population it is advisable to apply both self-contained research and the involvement of primary prevention and health promotion to research projects concerning health, social affairs, education, work and environment.

[Gender-sensitive epidemiological data analysis: methodological aspects and empirical outcomes. Illustrated by a health reporting example]. / Geschlechtergerechte epidemiologische Datenanalyse: Methodische Aspekte und empirische Befunde. Dargestellt an einem Beispiel aus der Gesundheitsberichterstattung.

In Germany gender-sensitive approaches are part of guidelines for good epidemiological practice as well as health reporting. They are increasingly claimed to realize the gender mainstreaming strategy in research funding by the federation and federal states. This paper focuses on methodological aspects of data analysis, as an empirical data example of which serves the health report of Bremen, a population-based cross-sectional study. Health reporting requires analysis and reporting methods that are able to discover sex/gender issues of questions, on the one hand, and consider how results can adequately be communicated, on the other hand. The core question is: Which consequences do a different inclusion of the category sex in different statistical analyses for identification of potential target groups have on the results? As evaluation methods logistic regressions as well as a two-stage procedure were exploratively conducted. This procedure combines graphical models with CHAID decision trees and allows for visualising complex results. Both methods are analysed by stratification as well as adjusted by sex/gender and compared with each other. As a result, only stratified analyses are able to detect differences between the sexes and within the sex/gender groups as long as one cannot resort to previous knowledge. Adjusted analyses can detect sex/gender differences only if interaction terms have been included in the model. Results are discussed from a statistical-epidemiological perspective as well as in the context of health reporting. As a conclusion, the question, if a statistical method is gender-sensitive, can only be answered by having concrete research questions and known conditions. Often, an appropriate statistic procedure can be chosen after conducting a separate analysis for women and men. Future gender studies deserve innovative study designs as well as conceptual distinctiveness with regard to the biological and the sociocultural elements of the category sex/gender.

Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren's syndrome.

BACKGROUND: B cell activation may result in an increased secretion of immunoglobulin free light chains (FLCs) in autoimmune diseases. OBJECTIVE: To analyse serum FLC levels in patients with rheumatoid arthritis and in those with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: Blood samples were collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and 139 patients with pSS. Serum FLC level was measured using a new quantitative immunoassay. RESULTS: Mean (standard error (SE)) serum kappa and lambda FLC levels were significantly higher in patients with rheumatoid arthritis and in those with pSS than in controls (kappa : 18.9 (1.1) and 16.3 (1.4) v 10.5 (0.4) mg/l, p<0.001 and p = 0.001, respectively; lambda: 16.7 (1.2) and 19.3 (1.5) v 11.6 (0.6) mg/l, p<0.001 for both). 18 (36%) patients with rheumatoid arthritis and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased kappa or lambda levels and abnormal ratio of kappa:lambda). Serum kappa and lambda levels were correlated with other B cell activation markers in both diseases. FLC levels increased with disease activity, because, unlike total gammaglobulin and immunoglobulin G levels, they were significantly correlated with Disease Activity Score 28 in patients with rheumatoid arthritis (p = 0.004 for kappa, p = 0.05 for lambda) and with extraglandular involvement in pSS (p = 0.01 for kappa, p = 0.04 for lambda). CONCLUSION: FLC levels are increased and correlate with disease activity in patients with rheumatoid arthritis and in those with pSS, two diseases in which increased risk of lymphoma could result from persistent B cell activation and disease activity. Further studies are required to determine whether FLC assessment could represent a relevant biomarker for response to treatment (especially B cell depletion) and for the risk of lymphoma in autoimmune diseases.

[Taking into consideration gender and sex. New chances to improve the quality of epidemiological and health research]. / Die Berücksichtigung der Geschlechterperspektive Neue Chancen für Qualitätsverbesserungen in Epidemiologie und Gesundheitsforschung.

Researchers who apply for project funding at the European level or at German Federal Ministries must take into account the gender aspects of their proposals as well as in the realization of these projects (gender mainstreaming) more and more often. The promotion of gender equality in research and science is becoming a "mainstream" task as well as a sign of the quality of the project. In practice, however, the process of carrying out gender sensitive research must still gain momentum. This article focuses on central questions and problems: Which are the gender aspects of a certain subject? In what way do we have to design studies and research methods to be able to apprehend and discover gender aspects properly? Which strategies of evaluation are adequate? What is the best way to analyze, interpret, and communicate data? The basics will be clarified (e. g. terms like sex/gender, doing gender, the role of the "gender" category in the context of social differentiation, causes and forms of gender bias). In addition, methodological/methodical hints and instruments to avoid distortion due to the inadequate consideration of gender category in the course of research will be introduced (diagnostic brief-questionnaire according to Eichler, gender-matrix, five challenges according to Doyal, gender adequate speech and publication).

Asbestos fibreyears and lung cancer: a two phase case-control study with expert exposure assessment.

AIMS: To assess the cumulative effect of asbestos on lung cancer risk where the exposure is assessed by an expert rating. METHODS: 1678 male cases and controls were enrolled in a population based matched case-control study, focused on occupational risk factors, carried out in West Germany. The exposure to asbestos was computed as lifelong working hours. For a validation subsample of 164 matched pairs from this study the intensity of asbestos exposure was further assessed by a panel of experts in order to obtain an estimate of the cumulative exposure on a time by intensity scale (fibreyears). The information on duration of asbestos exposure in the original study was combined with the fibreyears following the two phase case control study paradigm. RESULTS: The number of exposed subjects in the validation subsample was 75 cases and 71 controls. The percentage of subjects with a cumulative exposure < or =1, 1 to < or =10, and >10 fibreyears was 16%, 15%, and 15% for the cases and 18%, 16%, and 9% respectively for the controls. The smoking adjusted odds ratios for the fibreyears based on an unconditional logistic regression were 0.81, 1.02, and 1.60 respectively with increasing exposure categories (not significant). The coefficient (beta) for a log transformed trend was 1.156. Applying the two phase paradigm, these odds ratios became 0.86, 1.33, and 1.94; the latter reached significance and the beta coefficient was 1.178. CONCLUSIONS: The two phase paradigm allowed us to obtain a more precise estimate of the effect of asbestos on lung cancer. Results are consistent with a doubling of the lung cancer risk with 25 fibreyears asbestos exposure.

Undescended testis and the risk of testicular cancer: importance of source and classification of exposure information.

BACKGROUND: The strength of the association between undescended testis and testicular cancer varies considerably across studies. Here we report the effect of various classifications of self-reported history of undescended testis and different data sources on the estimates of the risk of testicular cancer from a case-control study. METHODS: We performed a population-based case-control study including 269 testicular cancer cases and 797 controls matched on age and region. Medical history was assessed by interviews (index persons) and mailed questionnaires (mothers). We used conditional logistic regression to calculate odds ratios (OR) and kappa coefficients to assess agreement between different sources of information. RESULTS: Odds ratios for testicular cancer ranged between 2.4 and 5.4 based on the sons' self-reports and between 1.1 and 1.9 based on the mothers' reports. The agreement between the sons and mothers on undescended, gliding or retractile testis was fair (kappa 0.53) and was good when these conditions were treated by surgery (kappa 0.89). The rating of a history of undescended testis by two urologists was fair (kappa 0.54). CONCLUSIONS: The questionnaire design, the classifications of undescended testis and data sources have an important impact on the OR for the association of undescended testis and testicular cancer. These factors may partially explain the heterogeneity of the OR for this association in case-control studies relying on self-reports.

Sorting the hype from the facts in testicular cancer: is testicular cancer related to trauma?

PURPOSE: The rate of testicular cancer is increasing. Trauma severe enough to cause testicular atrophy is a putative risk factor for testicular cancer but the epidemiological evidence is not conclusive. A population based, multicenter case-control study was performed from 1995 to 1997 to investigate potential risk factors for gonadal and extragonadal germ cell cancer. MATERIALS AND METHODS: The study was done in 5 German regions. Interviews were performed with 269 eligible male patients with a histologically verified diagnosis and 797 controls. Detailed information on medical and family history was collected at personal interviews. RESULTS: We identified a significantly elevated risk for testicular cancer in relation to testis and/or groin trauma (odds ratio 2.5, 95% confidence interval [CI] 1.51 to 4.20). After introducing a lag time by excluding reports of trauma within the last 12 months before diagnosis or interview the corresponding odds ratio was 2.1 (95% CI 1.24 to 3.61). Analysis of the circumstances and the reported types of injury allowed us to restrict the study to testis trauma specifically, which had an odds ratio of 3.49 (95% CI 1.78 to 6.81). To account for a potential reporting bias analysis was restricted to traumatic episodes for which medical attention was sought. This restriction resulted in an odds ratio of 0.70 (95% CI 0.19 to 2.63) after excluding from study trauma reports within the last 12 months. CONCLUSIONS: The results of our study do not support the hypothesis that testicular trauma is an important risk factor for testicular cancer. The possibility of recall bias should be considered.

Aggregation of lung cancer in families: results from a population-based case-control study in Germany.

The authors investigated familial aggregation of lung cancer by means of a population-based case-control study, conducted in Germany between 1988 and 1993. They compared lung cancer prevalence in first degree relatives of 945 patients and 983 controls, accounting for various potential risk factors using logistic regression and generalized estimating equations. Some 83% of the study participants were male, and about 14% were below age 51 (young age group). Overall, lung cancer in parents or siblings was associated with a 1.67-fold (95% confidence interval (CI): 1.11, 2.52) increase in lung cancer risk. For the young participants, this risk was 4.75 (95% CI: 1.20, 18.77). Having multiple affected relatives (two or more) was related to a threefold risk elevation (odds ratio (OR) = 2.99, 95% CI: 0.32, 27.55). Paternal (OR = 1.64, 95% CI: 0.91, 2.96) but not maternal (OR = 0.91, 95% CI: 0.32, 2.61) lung cancer was associated with an increased risk of the disease. Lung cancer risk from smoking was particularly pronounced in the parents of cases (OR = 12.20, 95% CI: 3.34, 44.62 vs. OR = 7.93, 95% CI: 2.43, 25.91 in parents of controls). No risk elevation was detected for other smoking-related and other cancers in general. Results confirm previous findings and support the etiologic role of a genetic predisposition to lung cancer.