Bringing Anatomical Information into Neuronal Network Models.

For constructing neuronal network models computational neuroscientists have access to wide-ranging anatomical data that nevertheless tend to cover only a fraction of the parameters to be determined. Finding and interpreting the most relevant data, estimating missing values, and combining the data and estimates from various sources into a coherent whole is a daunting task. With this chapter we aim to provide guidance to modelers by describing the main types of anatomical data that may be useful for informing neuronal network models. We further discuss aspects of the underlying experimental techniques relevant to the interpretation of the data, list particularly comprehensive data sets, and describe methods for filling in the gaps in the experimental data. Such methods of "predictive connectomics" estimate connectivity where the data are lacking based on statistical relationships with known quantities. Exploiting organizational principles that link the plethora of data in a unifying framework can be useful for informing computational models. Besides overarching principles, we touch upon the most prominent features of brain organization that are likely to influence predicted neuronal network dynamics, with a focus on the mammalian cerebral cortex. Given the still existing need for modelers to navigate a complex data landscape full of holes and stumbling blocks, it is vital that the field of neuroanatomy is moving toward increasingly systematic data collection, representation, and publication.

Feasibility of CT quantification of intratumoural 166Ho-microspheres.

BACKGROUND: Microspheres loaded with radioactive 166Ho (166Ho-MS) are novel particles for radioembolisation and intratumoural treatment. Because of the limited penetration of ß radiation, quantitative imaging of microsphere distribution is crucial for optimal intratumoural treatment. Computed tomography (CT) may provide high-resolution and fast imaging of the distribution of these microspheres, with lower costs and widespread availability in comparison with current standard single-photon emission tomography (SPECT) and magnetic resonance imaging. This phantom study investigated the feasibility of CT quantification of 166Ho-MS. METHODS: CT quantification was performed on a phantom with various concentrations of HoCl and Ho-MS to investigate the CT sensitivity and calibrate the CT recovery. 166Ho-MS were injected into ex vivo tissues, in VX-2 cancer-bearing rabbits, and in patients with head-neck cancer, to demonstrate sensitivity and clinical visibility. The amount of Ho-MS was determined by CT scanning, using a density-based threshold method and compared with a validated 166Ho SPECT quantification method. RESULTS: In the phantom, a near perfect linearity (least squares R2 > 0.99) between HU values and concentration of 166Ho was found. Ex vivo tissue experiments showed an excellent correlation (r = 0.99, p < 0.01) between the dose calibrator, SPECT, and CT imaging. CT recovery was on average 86.4% ex vivo, 76.0% in rabbits, and 99.1% in humans. CONCLUSION: This study showed that CT-based quantification of Ho microspheres is feasible and is a high-resolution alternative to SPECT-based determination of their local distribution.

Intratumoral injection of radioactive holmium ( 166 Ho) microspheres for treatment of oral squamous cell carcinoma in cats.

BACKGROUND & AIMS: A "microbrachytherapy" was developed as treatment option for inoperable tumours by direct intratumoral injection of radioactive holmium-166 ( 166 Ho) microspheres (MS). 166 Ho emits ß-radiation which potentially enables a high, ablative, radioactive-absorbed dose on the tumour tissue while sparing surrounding tissues. MATERIALS & METHODS: Safety and efficacy of 166 Ho microbrachytherapy were evaluated in a prospective cohort study of 13 cats with inoperable oral squamous cell carcinoma without evidence of distant metastasis. RESULTS: Local response rate was 55%, including complete response or partial response (downstaging) enabling subsequent marginal resection. Median survival time was 113 days overall, and 296 days for patients with local response. Side effects were minimal. Tumour volume was a significant predictor of response. DISCUSSION: Response rate may be further improved by optimizing the intratumoral spatial distribution of 166 Ho MS. CONCLUSION: 166 Ho microbrachytherapy has potential as a minimally invasive, single procedure radio-ablation treatment of unresectable tumours with minimal morbidity.

[Systematic review of the side effects of benzodiazepines]. / Aandacht voor bijwerkingen van benzodiazepinen is belangrijk: een systematisch overzicht.

- Benzodiazepines are used frequently, despite the risk of severe side effects.- The Generic module 'Side effects; prevention, monitoring and treatment of side effects of drugs for psychiatric disorders' will be published soon. This contains recommendations for reduction in the risk for falls and fractures, cognitive problems and dependency related to the use of benzodiazepines or Z-drugs (zopiclone, zolpidem).- Prescribing physicians and pharmacists are compulsorily required to provide extensive information to patients on the anticipated effects and side effects of benzodiazepines, and on the limited prescription period.- A lot of information has become available from systematic literature reviews by the Benzodiazepines working group. Different benzodiazepines present similar risks of falls and fractures; higher doses present a higher risk, and Z-drugs are no safer.- In comparison with placebo, benzodiazepines and Z-drugs soon cause cognitive problems, even at low doses and in drugs with a short half-life. There is almost no development of tolerance for these cognitive problems.- Tailored patient education letters for ceasing benzodiazepine use are more effective than the standard letters. Different dose-tapering schemes have comparable success rates (on average 50%). Augmentation with cognitive behavioural therapy is effective for dose reduction.- It is therefore important to carefully consider the use of benzodiazepines before using them.

Sexual distress and associated factors among cervical cancer survivors: A cross-sectional multicenter observational study.

BACKGROUND: To assess whether sexual distress among cervical cancer (CC) survivors is associated with frequently reported vaginal sexual symptoms, other proposed biopsychosocial factors and whether worries about painful intercourse mediate the relation between vaginal sexual symptoms and sexual distress. METHODS: A cross-sectional study was conducted among 194 sexually active partnered CC survivors aged 25 to 69 years. Sexual distress, vaginal sexual symptoms, sexual pain worry, anxiety, depression, body image concerns, and relationship dissatisfaction and the sociodemographic variables age, time since treatment, and relationship duration were assessed by using validated self-administrated questionnaires. RESULTS: In total, 33% (n = 64) of the survivors scored above the cut-off score for sexual distress. Higher levels of sexual distress were shown to be associated with higher levels of vaginal sexual symptoms, sexual pain worry, relationship dissatisfaction, and body image concerns. Furthermore, the results showed that sexual pain worry partly mediated the association between vaginal sexual symptoms and sexual distress, when controlling for relationship dissatisfaction and body image concerns. CONCLUSIONS: Appropriate rehabilitation programs should be developed for CC survivors to prevent and reduce not only vaginal sexual symptoms but also sexual pain worry, relationship dissatisfaction, and body image concerns to reduce sexual distress.

A nurse-led sexual rehabilitation intervention after radiotherapy for gynecological cancer.

PURPOSE: Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. METHODS: Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). RESULTS: Twenty participants were 26-71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. CONCLUSIONS: According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial.

HPV-negative squamous cell carcinoma of the anal canal is unresponsive to standard treatment and frequently carries disruptive mutations in TP53.

BACKGROUND: Human papillomavirus (HPV), p16 expression, and TP53 mutations are known prognostic factors in head and neck squamous cell carcinoma, but their role in squamous cell carcinoma of the anal canal (SCCAC) is less well established. The objective of this study was to determine the prognostic significance of tumour HPV status, p16 and p53 expression, and mutations in TP53 in patients with SCCAC receiving (chemo)radiotherapy. METHODS: Human papillomavirus DNA was determined using an INNO-LiPA-based assay in tumour tissue of 107 patients with locally advanced SCCAC. Patients were treated with radiotherapy, with or without concurrent chemotherapy consisting of a fluoropyrimidine and mitomycin C. Expression of p16 and p53 was determined using immunohistochemistry. Exons 2-11 of TP53 in tumour tissue were sequenced. RESULTS: DNA of high-risk HPV types was detected in 93 out of 107 tumours (87%), all of which overexpressed p16 (HPV+/p16+). Of 14 HPV-negative (HPV-) tumours (13%), 10 (9%) were p16-negative (HPV-/p16-) and 4 (4%) overexpressed p16 (HPV-/p16+). Patients with HPV-/p16- disease had inferior 3-year locoregional control (LRC) (15%) compared with patients with HPV+/p16+ tumours (82%, P<0.001) and HPV-/p16+ tumours (75%, P=0.078). Similarly, 3-year overall survival (OS) was 35% (HPV-/p16-) vs 87% (HPV+/p16+, P<0.001) and 75% (HPV-/p16+, P=0.219). Disruptive mutations in TP53 were found in 80% of HPV-/p16- tumours vs 6% of HPV+/p16+ tumours (P<0.001). In multivariate analysis, HPV-/p16- status was an independent predictor of inferior LRC and OS. CONCLUSIONS: HPV- tumours are frequently TP53 mutated. HPV-/p16- status is a strong predictor for reduced LRC and OS, and alternative treatment strategies for patients with HPV-/p16- disease need to be explored.

Effect of Chinese herbs on CYP3A4 activity and expression in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has become more popular among cancer patients in the Western world, who often use Chinese herbs as adjuvant therapy to reduce the adverse effects of conventional chemotherapy. However, pharmacokinetic (PK) interactions between Chinese herbs and anticancer drugs can occur and have dramatic consequences for these patients. Currently, only a few possible PK interactions between Chinese herbs and conventional Western drugs have been documented. AIM OF THE STUDY: Since the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) contributes to most of the PK interactions with (anticancer) drugs, the effect of four Chinese herbs (Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus) on the activity and expression of CYP3A4 was investigated in vitro. MATERIALS AND METHODS: Ethanol and water-ethanol extracts of the four Chinese herbs were prepared from raw material. CYP3A4 inhibition was assessed by the use of Supersomes™ in a fluorescence assay. Furthermore, CYP3A4 induction was evaluated in a human pregnane X receptor (hPXR)-mediated CYP3A4 reporter gene assay and a quantitative real time PCR assay, both in human colon adenocarcinoma-derived LS180 cells (LS180). RESULTS: Extracts of Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus inhibited CYP3A4 in human CYP3A4 Supersomes™ (IC50 values: 17-83 µg/mL). Oldenlandia diffusa and Rehmannia glutinosa significantly induced PXR-mediated CYP3A4 (p<0.001). Oldenlandia diffusa also significantly induced CYP3A4 mRNA levels (p<0.001 at 250 µg/mL). CONCLUSIONS: Concomitant use of Oldenlandia diffusa and Rehmannia glutinosa could result in induction of CYP3A4, leading to a reduced efficacy of drugs that are CYP3A4 substrates and have a narrow therapeutic window. Because of the possible enhanced toxicity caused by CYP3A4 inhibition, clinical effects of CYP3A4 inhibition by Astragalus propinquus and Codonopsis tangshen must also be taken into account. In conclusion, herb-drug interactions between Chinese herbs and various CYP3A4 substrates can occur. Further research to investigate the clinical relevance of the interactions caused by Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus is required.

Development and validation of a LC-MS/MS method for the in vitro analysis of 1-hydroxymidazolam in human liver microsomes: application for determining CYP3A4 inhibition in complex matrix mixtures.

Complementary and alternative medicines (CAM) can affect the pharmacokinetics of anticancer drugs by interacting with the metabolizing enzyme cytochrome P450 (CYP) 3A4. To evaluate changes in the activity of CYP3A4 in patients, levels of 1-hydroxymidazolam in plasma are often determined with liquid chromatography-quadrupole mass spectrometry (LC-MS/MS). However, validated LC-MS/MS methods to determine in vitro CYP3A4 inhibition in human liver microsomes are scarce and not optimized for evaluating CYP3A4 inhibition by CAM. The latter is necessary because CAM are often complex mixtures of numerous compounds that can interfere with the selective measurement of 1-hydroxymidazolam. Therefore, the aim was to validate and optimize an LC-MS/MS method for the adequate determination of CYP3A4 inhibition by CAM in human liver microsomes. After incubation of human liver microsomes with midazolam, liquid-liquid extraction with tert-butyl methyl ether was applied and dried samples were reconstituted in 50% methanol. These samples were injected onto a reversed-phase chromatography consisting of a Zorbax Extend-C18 column (2.1 × 150 mm, 5.0 µm particle size), connected to a triple quadrupole mass spectrometer with electrospray ionization. The described LC-MS/MS method was validated over linear range of 1.0-500 nm for 1-hydroxymidazolam. The results revealed good inter-assay accuracy (≥85% and ≤115%) and within-day and between-day precisions (coefficient of variation ≤ 4.43%). Furthermore, the applicability of this assay for the determination of CYP3A4 inhibition in complex matrix mixtures was successfully demonstrated in an in vitro experiment in which CYP3A4 inhibition by known CAM (ß-carotene, green tea, milk thistle and St. John's wort) was determined.

Biodiesel and biohydrogen production from cotton-seed cake in a biorefinery concept.

Biodiesel production from cotton-seed cake (CSC) and the pretreatment of the remaining biomass for dark fermentative hydrogen production was investigated. The direct conversion to biodiesel with alkali free fatty acids neutralization pretreatment and alkali transesterification resulted in a biodiesel with high esters content and physicochemical properties fulfilling the EN-standards. Blends of cotton-seed oil methyl esters (CME) and diesel showed an improvement in lubricity and cetane number. Moreover, CME showed good compatibility with commercial biodiesel additives. On the basis of conversion of the remaining CSC to sugars fermentable towards hydrogen, the optimal conditions included removal of the oil of CSC and pretreatment at 10% NaOH (w/w dry matter). The extreme thermophilic bacterium Caldicellulosiruptor saccharolyticus showed good hydrogen production, 84-112% of the control, from NaOH-pretreated CSC and low hydrogen production, 15-20% of the control, from the oil-rich and not chemically pretreated CSC, and from Ca(OH)2-pretreated CSC.

PXR-mediated P-glycoprotein induction by small molecule tyrosine kinase inhibitors.

The rapid development of drug resistance as a result of exposure to small molecule tyrosine kinase inhibitors (TKIs) is an important drawback to the successful use of these agents in the clinic. Although one of the most established mechanisms by which cells acquire drug resistance to anticancer drugs is the up regulation of drug efflux transporters such as P-glycoprotein (PGP), it is currently still unknown whether TKIs have the propensity to induce PGP. The effect of TKIs on the protein expression and activity of PGP was assessed after treatment of LS180 cells with clinically relevant concentrations of the TKIs. In addition, the involvement of the nuclear pregnane X receptor (PXR), a known regulator of PGP expression, was determined. At least five out of the nine tested TKIs (erlotinib, gefitinib, nilotinib, sorafenib, vandetanib) were able to induce the expression of PGP within 48 h in LS180 cells. Accordingly, these TKIs were also shown to affect the accumulation of a P-glycoprotein specific probe substrate. Furthermore, we showed that the pregnane X receptor (PXR), which is an important regulator of PGP induction, is involved in the upregulation of PGP protein expression following exposure to these TKIs. Our data show that PXR-mediated upregulation of PGP expression by TKIs might be a possible mechanism underlying acquired drug resistance in cancer cells.

Integration of first and second generation biofuels: fermentative hydrogen production from wheat grain and straw.

Integrating of lignocellulose-based and starch-rich biomass-based hydrogen production was investigated by mixing wheat straw hydrolysate with a wheat grain hydrolysate for improved fermentation. Enzymatic pretreatment and hydrolysis of wheat grains led to a hydrolysate with a sugar concentration of 93.4 g/L, while dilute-acid pretreatment and enzymatic hydrolysis of wheat straw led to a hydrolysate with sugar concentration 23.0 g/L. Wheat grain hydrolysate was not suitable for hydrogen production by the extreme thermophilic bacterium Caldicellulosiruptor saccharolyticus at glucose concentrations of 10 g/L or higher, and wheat straw hydrolysate showed good fermentability at total sugar concentrations of up to 10 g/L. The mixed hydrolysates showed good fermentability at the highest tested sugar concentration of 20 g/L, with a hydrogen production of 82-97% of that of the control with pure sugars. Mixing wheat grain hydrolysate with wheat straw hydrolysate would be beneficial for fermentative hydrogen production in a biorefinery.

Bridging between professionals in perinatal care: towards shared care in the Netherlands.

Relatively high perinatal mortality rates in the Netherlands have required a critical assessment of the national obstetric system. Policy evaluations emphasized the need for organizational improvement, in particular closer collaboration between community midwives and obstetric caregivers in hospitals. The leveled care system that is currently in place, in which professionals in midwifery and obstetrics work autonomously, does not fully meet the needs of pregnant women, especially women with an accumulation of non-medical risk factors. This article provides an overview of the advantages of greater interdisciplinary collaboration and the current policy developments in obstetric care in the Netherlands. In line with these developments we present a model for shared care embedded in local 'obstetric collaborations'. These collaborations are formed by obstetric caregivers of a single hospital and all surrounding community midwives. Through a broad literature search, practical elements from shared care approaches in other fields of medicine that would suit the Dutch obstetric system were selected. These elements, focusing on continuity of care, patient centeredness and interprofessional teamwork form a comprehensive model for a shared care approach. By means of this overview paper and the presented model, we add direction to the current policy debate on the development of obstetrics in the Netherlands. This model will be used as a starting point for the pilot-implementation of a shared care approach in the 'obstetric collaborations', using feedback from the field to further improve it.

Impact of wind turbine sound on annoyance, self-reported sleep disturbance and psychological distress.

PURPOSE OF THE RESEARCH: The present government in the Netherlands intends to realize a substantial growth of wind energy before 2020, both onshore and offshore. Wind turbines, when positioned in the neighborhood of residents may cause visual annoyance and noise annoyance. Studies on other environmental sound sources, such as railway, road traffic, industry and aircraft noise show that (long-term) exposure to sound can have negative effects other than annoyance from noise. This study aims to elucidate the relation between exposure to the sound of wind turbines and annoyance, self-reported sleep disturbance and psychological distress of people that live in their vicinity. Data were gathered by questionnaire that was sent by mail to a representative sample of residents of the Netherlands living in the vicinity of wind turbines PRINCIPAL RESULTS: A dose-response relationship was found between immission levels of wind turbine sound and selfreported noise annoyance. Sound exposure was also related to sleep disturbance and psychological distress among those who reported that they could hear the sound, however not directly but with noise annoyance acting as a mediator. Respondents living in areas with other background sounds were less affected than respondents in quiet areas. MAJOR CONCLUSIONS: People living in the vicinity of wind turbines are at risk of being annoyed by the noise, an adverse effect in itself. Noise annoyance in turn could lead to sleep disturbance and psychological distress. No direct effects of wind turbine noise on sleep disturbance or psychological stress has been demonstrated, which means that residents, who do not hear the sound, or do not feel disturbed, are not adversely affected.

Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors.

AIMS: Empagliflozin is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study assessed pharmacological properties of empagliflozin in vitro and pharmacokinetic properties in vivo and compared its potency and selectivity with other SGLT-2 inhibitors. METHODS: [(14)C]-alpha-methyl glucopyranoside (AMG) uptake experiments were performed with stable cell lines over-expressing human (h) SGLT-1, 2 and 4. Two new cell lines over-expressing hSGLT-5 and hSGLT-6 were established and [(14)C]-mannose and [(14)C]-myo-inositol uptake assays developed. Binding kinetics were analysed using a radioligand binding assay with [(3)H]-labelled empagliflozin and HEK293-hSGLT-2 cell membranes. Acute in vivo assessment of pharmacokinetics was performed with normoglycaemic beagle dogs and Zucker diabetic fatty (ZDF) rats. RESULTS: Empagliflozin has an IC(50) of 3.1 nM for hSGLT-2. Its binding to SGLT-2 is competitive with glucose (half-life approximately 1 h). Compared with other SGLT-2 inhibitors, empagliflozin has a high degree of selectivity over SGLT-1, 4, 5 and 6. Species differences in SGLT-1 selectivity were identified. Empagliflozin pharmacokinetics in ZDF rats were characterised by moderate total plasma clearance (CL) and bioavailability (BA), while in beagle dogs CL was low and BA was high. CONCLUSIONS: Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the highest selectivity window of the tested SGLT-2 inhibitors over hSGLT-1. Empagliflozin represents an innovative therapeutic approach to treat diabetes.

Effect of pretreatment severity on the conversion of barley straw to fermentable substrates and the release of inhibitory compounds.

The production of fermentable substrates from barley straw under various process conditions was studied. Pretreatment included chemical pretreatment with dilute-acid followed by enzymatic hydrolysis; the pretreatment conditions were expressed in a combined severity factor, CS, which ranged in the present study from -1.6 to 1.1. Considering the production of fermentable sugars and the release of inhibitory compounds, the optimal pretreatment conditions were 170°C, 0% sulfuric acid and 60 min, corresponding to CS -0.4. Under these conditions, 21.4 g glucose/L, 8.5 g xylose/L, and 0.5 g arabinose/L were produced, while 0.1g HMF/L, 0.4 g furfural/L, 0.0 g levulinic acid/L, 0.0 g formic acid/L, and 2.1g acetic acid/L were released. The ratio of Σ sugars/Σ inhibitors proved to be a good tool for evaluating the suitability of a hydrolysate for fermentation purposes.

Dose-response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight, preterm birth and small for gestational age (SGA)-a systematic review and meta-analyses.

BACKGROUND: Descriptions of the effects of moderate alcohol consumption during pregnancy on adverse pregnancy outcomes have been inconsistent. OBJECTIVE: To review systematically and perform meta-analyses on the effect of maternal alcohol exposure on the risk of low birthweight, preterm birth and small for gestational age (SGA). SEARCH STRATEGY: Using Medical Subject Headings, a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science between 1 January 1980 and 1 August 2009 was performed followed by manual searches. SELECTION CRITERIA: Case-control or cohort studies were assessed for quality (STROBE), 36 available studies were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the information on low birthweight, preterm birth and SGA using a standardised protocol. Meta-analyses on dose-response relationships were performed using linear as well as first-order and second-order fractional polynomial regressions to estimate best fitting curves to the data. MAIN RESULTS: Compared with abstainers, the overall dose-response relationships for low birthweight and SGA showed no effect up to 10 g pure alcohol/day (an average of about 1 drink/day) and preterm birth showed no effect up to 18 g pure alcohol/day (an average of 1.5 drinks/day); thereafter, the relationship showed a monotonically increasing risk for increasing maternal alcohol consumption. Moderate consumption during pre-pregnancy was associated with reduced risks for all outcomes. CONCLUSIONS: Dose-response relationship indicates that heavy alcohol consumption during pregnancy increases the risks of all three outcomes whereas light to moderate alcohol consumption shows no effect. Preventive measures during antenatal consultations should be initiated.

The impact of mobility on HIV control: a modelling study.

Mobility is associated with HIV due to more risky sexual behaviour of mobile groups such as travellers and migrants. Limited participation of such groups may reduce the effectiveness of HIV interventions disproportionally. The established STDSIM model, which simulates transmission and control of HIV and STD, was extended to simulate mobility patterns based on data from Tanzania. We explored the impact of non-participation of mobile groups (travellers and recent migrants) on the effectiveness of two interventions: condom promotion and health education aiming at partner reduction. If mobile groups do not participate, the effectiveness of both interventions could be reduced by 40%. The impact of targeting travellers with a combined HIV campaign is close to that of a general population intervention. In conclusion, it is important to account for possible non-participation of migrants and travellers. If non-participation is substantial, impact of interventions can be greatly improved by actively approaching these people.

Explaining differences in birth outcomes in relation to maternal age: the Generation R Study.

OBJECTIVE: To examine the association between maternal age and birth outcomes, and to investigate the role of sociodemographic and lifestyle-related determinants. DESIGN: Population-based prospective cohort study from early pregnancy onwards. SETTING: Rotterdam, the Netherlands. POPULATION: A cohort of 8568 mothers and their children. METHODS: Maternal age was assessed at enrolment. Information about sociodemographic (height, weight, educational level, ethnicity, parity) and lifestyle-related determinants (alcohol consumption, smoking habits, folic acid supplement use, caffeine intake, daily energy intake) and birth outcomes was obtained from questionnaires and hospital records. Multivariate linear and logistic regression analyses were used. MAIN OUTCOMES MEASURES: Birthweight, preterm delivery, small-for-gestational-age, and large-for-gestational-age. RESULTS: As compared with mothers aged 30-34.9 years, no differences in risk of preterm delivery were found. Mothers younger than 20 years had the highest risk of delivering small-for-gestational-age babies(OR 1.6, 95% CI: 1.1-2.5); however, this increased risk disappeared after adjustment for sociodemographic and lifestyle-related determinants. Mothers older than 40 years had the highest risk of delivering large-for-gestational-age babies (OR 1.3, 95% CI: 0.8-2.4). The associations of maternal age with the risks of delivering large-for-gestational-age babies could not be explained by sociodemographic and lifestyle-related determinants. CONCLUSIONS: As compared with mothers aged 30-34.9 years, younger mothers have an increased risk of small-for-gestational-age babies, whereas older mothers have an increased risk of large-for-gestational-age babies. Sociodemographic and lifestyle-related determinants cannot fully explain these differences.