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.

[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.

[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.

[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 - 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.

[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.

Cigar and pipe smoking and lung cancer risk: a multicenter study from Europe.

BACKGROUND: Because limited information is available on the quantitative association between consumption of tobacco products other than cigarettes and lung cancer risk, we undertook a case-control study of this relationship. METHODS: We investigated lung cancer risk among smokers of cigars and/or cigarillos only and of pipes only and compared these risks with the risk of smokers of cigarettes only in a case-control study conducted in seven European areas. Our study population consisted of 5621 male case patients with lung cancer and 7255 male control subjects. Each subject or his proxy was interviewed with respect to the subject's smoking history and other risk factors for lung cancer. RESULTS: The odds ratio (OR) for smoking cigars and cigarillos only was 9.0 (95% confidence interval [CI] = 5.8-14.1), based on 43 exposed case patients and 77 exposed control subjects, and the OR for smoking a pipe only was 7.9 (95% CI = 5.3-11.8), representing 61 case patients and 129 control subjects. The OR for smoking cigarettes only was 14.9 (95% CI = 12.3-18.1), based on 4204 case patients and 3930 control subjects. A dose-response relationship was present for duration of use and cumulative consumption both for cigars and cigarillos and for pipe tobacco. An effect was also suggested for inhalation of cigar and cigarillo smoke. The dose-response relationships between lung cancer risk and either duration of smoking or average and cumulative consumption were similar for cigar and cigarillo smoking, pipe smoking, and cigarette smoking. CONCLUSION: Our results suggest that smoking of European cigars, cigarillos, and pipe tobacco might exert a carcinogenic effect on the lung comparable to that of cigarettes.

DNA methylation and the origin of complement factor B polymorphism.

BF is a polymorphic complement component encoded in the MHC. In each of two frequent alleles of BF, BF*FA and BF*FB, the difference in relation to the major allele BF*S has been shown to consist in the nonsynonymous substitution of only one base of the coding sequence. Both substitutions occur within the same codon and affect contiguous positions, corresponding to the dinucleotide CpG in BF*S. We propose here that BF*FA and BF*FB arose independently from BF*S by the frequently described transition mutations associated with cytosine methylation at CpG sites. By probing sperm DNA with methylation-sensitive restriction enzymes, we obtained experimental evidence of germ line methylation of the CpG site considered. The dinucleotide of the BF gene probably constitutes a site for recurrent mutation, and this is of relevance for the use of BF as a genetic marker, and the origin of forms of the protein with altered functional properties.

Human factor B. Complete cDNA sequence of the BF*S allele.

The gene of human complement factor B (BF) is located within the class III region of the major histocompatibility complex. The knowledge of the coding sequence of the BF gene rests on a set of partial sequence studies reported by various sources, and full-length sequences ascribed to specific alleles of this polymorphic complement component have not yet been published. Now, we have isolated and sequenced a collection of cDNA clones derived from BF*S, the major BF allele. We present an uninterrupted, allele-specific sequence of the entire coding region and the 3' untranslated segment of the cDNA. Extensive comparison of this and previously available sequence data was carried out, and a number of base substitutions were observed in relation to some of the earlier sequences. The possibility that these differences arise from polymorphism in the BF gene is discussed.

Occupational risk factors for lung cancer: a case-control study in West Germany.

BACKGROUND: The aim of this study is to evaluate carcinogens and occupations suspected to cause lung cancer and to generate new hypotheses about occupational risks. METHODS: In a hospital-based study 1004 incident lung cancer cases and the same number of population controls matched for region, sex and age were interviewed between 1988 and 1993 for their smoking and occupational history. Exposure assessment was based on 33 job-specific supplementary questionnaires. Conditional logistic regression was used to calculate odds ratios (OR) and to control for smoking and occupational asbestos exposure. RESULTS: Lifelong prevalence of exposure to asbestos was 20.5% for exposure of more than 940 lifetime working hours among controls, corresponding to an OR of 1.62 (95% confidence interval [CI] : 1.28-2.05) that was reduced to 1.45 after adjustment for smoking (P < 5%). Statistically elevated risks after adjustment for smoking and asbestos were seen in metal production and processing workers, transportation workers and freight handlers, in the rubber and plastics industry, in metal production, in engine and vehicle building, and installation. Significantly increased OR after adjustment for smoking and asbestos that deserve further attention were seen in plastics processing workers (OR = 3.49), and sheet and structural metal workers (OR = 2.01 and 2.37, respectively). CONCLUSIONS: The results of the study confirm previously described occupational risks. Because of the possibility of controlling for occupational asbestos exposure, the study gives clear indications for prevention and further research.

Occupational and environmental hazards associated with lung cancer.

In a hospital-based case-control study 194 lung cancer cases, 194 hospital controls, and 194 population controls were interviewed for their smoking, occupational, and residential history by trained interviewers, using a standardized questionnaire. In order to include many different environmental exposures, case ascertainment took place in seven different hospitals with catchment areas ranging from rural to highly industrialized. Lung cancer risk strongly increases with cumulative cigarette dose, reaching an odds ratio (OR) of 16.19 (95% confidence limits (CL): 5.10, 51.33) for male smokers of more than 40 pack-years and an OR of 19.99 (95% CL: 4.98, 80.24) for female smokers of more than 20 pack-years. For the quantification of occupational exposure to known carcinogens of the lung a novel approach was developed which accumulates exposure information obtained by supplemental questionnaires through an automatic procedure. The OR for the highest exposure group in males was 2.7 (95% CL: 1.23, 5.78). Significantly increased risks were observed in the metal industry, particularly in smelter and foundry workers (OR 4.8, 95% CL: 1.15, 20.16) and in turners (OR 2.2, 95% CL: 1.05, 4.75). In the construction industry the risks were particularly high in road construction workers (OR 3.7, 95% CL: 1.06, 13.20) and in unskilled construction workers (OR 2.7, 95% CL: 1.24, 5.76). The risks in these occupational groups increased with duration and with latency. Quantification of air pollution was done on a county basis by time period. An index based on emission data for sulphur dioxide was compared to a semiquantitative index, which included additional information on ambient air pollution. After adjustment for smoking and occupational exposures an OR of 1.01 (95% CL: 0.53, 1.91) for an emission index and of 1.16 (95% CL: 0.64, 2.13) for a semiquantitative index was obtained.

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.

Occupational life course and lung cancer risk in men. Findings from a socio-epidemiological analysis of job-changing histories in a case-control study.

Psychosocial factors in general, and the social and psychological conditions of work and occupation in particular, have attracted little attention to the epidemiological investigation into the occupational-related causes of lung cancer. There is some evidence available concerning the impact of loss events--including job losses--on cancer development. During our research presented in this article, we examined job changes and job transitions in the occupational biography of men with regard to their circumstances in terms of (in-)voluntariness both as individual events and the job-changing histories of individuals. We expected the job-changing histories of lung cancer cases to be more involuntary than those of population controls, and vice versa. Our sample contains 391 male case-control pairs. Cases are defined as newly-diagnosed men of German nationality with a histologically- or cytologically-confirmed diagnosis of primary lung cancer. Population controls were drawn randomly from the municipality records of residents and individuals matched to cases 1:1 by age and region. Occupational histories were reconstructed, and information about other classical and suspected risk factors was collected during standardized interviews by trained interviewers. We categorized the reported reasons for job changes, and classified them with respect to voluntariness on a seven-stepped rating scale from -3 'very involuntary' to +3 'very voluntary', defining relations within the empirically established categories. The job-changing histories of individuals are described by using the average score of voluntariness. We measured the degree of voluntariness for the occupational history: (1) by the rounded average score; and (2) by the quintiles of the average score. On the basis of individuals matched odds ratios (OR) estimates are derived for the score of voluntariness unadjusted and adjusted for smoking, asbestos exposure and socio-economic group by conditional logistic regression. The investigation into job-changing histories using the average score of voluntariness lead to similar results for both measuring methods for the total study group. When the rounded score was used, job-changing histories which were assessed as 'very involuntary' and 'involuntary' (score -3 and -2) showed an elevated odds ratio of adjusted 1.41 (95%-CI: 0.57; 3.48), and when they were assessed as 'moderately involuntary' (score -1) the adjusted odds ratio was 1.59 (95%-CI: 1.02; 2.48), as compared with job-changing histories assessed as neutral (score 0). When the degree of voluntariness was measured by quintiles, the first quintile (score -3- < -0.6) showed an elevated risk of adjusted OR 1.36 (95%-CI: 0.79; 2.36) as compared to the third quintile (score -0.2- < -0.1).(ABSTRACT TRUNCATED AT 400 WORDS)

[Female life courses and health--results of a study of national survey data of 50-69-year-old women in East and West Germany]. / Weibliche Lebensverläufe und Gesundheit--Ergebnisse einer Untersuchung nationaler Surveydaten 50-69jähriger Frauen aus Ost- und Westdeutschland.

The aim of the study was to examine the impact of different forms of combining family and paid work on the health status of women. The study was a secondary analysis of cross-sectional data from the National Health Survey and included 1530 women, aged 50 to 69 years, from East and West Germany. Three groups were composed to describe different forms of family and occupation in the life course (family or occupational career, combination of family and occupation). Additionally, aspects of the social situation, resources and burdens as well as indicators of health behaviour were included in the analyses. The most remarkable result was a significantly worse state of health of employed and childless women (occupational career), aged 50 to 59 years. This finding remained after adjustment for different potential factors of influence. Considering the increasing proportion of women without children in modern societies, longitudinal analyses would be necessary to investigate the long term effect of familial and occupational factors on the health status of women.