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Usutu virus (USUV) is an emerging flavivirus that can infect birds and mammals. In humans, in severe cases, it may cause neuroinvasive disease. The innate immune system, and in particular the interferon response, functions as the important first line of defense against invading pathogens such as USUV. Many, if not all, viruses have developed mechanisms to suppress and/or evade the interferon response in order to facilitate their replication. The ability of USUV to antagonize the interferon response has so far remained largely unexplored. Using dual-luciferase reporter assays we observed that multiple of the USUV nonstructural (NS) proteins were involved in suppressing IFN-β production and signaling. In particular NS4A was very effective at suppressing IFN-β production. We found that NS4A interacted with the mitochondrial antiviral signaling protein (MAVS) and thereby blocked its interaction with melanoma differentiation-associated protein 5 (MDA5), resulting in reduced IFN-β production. The TM1 domain of NS4A was found to be essential for binding to MAVS. By screening a panel of flavivirus NS4A proteins we found that the interaction of NS4A with MAVS is conserved among flaviviruses. The increased understanding of the role of NS4A in flavivirus immune evasion could aid the development of vaccines and therapeutic strategies.

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

Membrane distillation (MD) is considered the most suitable process for small-scale seawater desalination to augment fresh water supply in remote areas. In this study, a pilot seawater MD desalination process was trialled for potable water supply on a remote and isolated island in Vietnam. The pilot MD system was based on air gap membrane distillation (AGMD), which is considered the most energy-efficient configuration of MD. The AGMD configuration allowed for the utilization of the latent heat of water vapor condensation to pre-heat the seawater feed, thus reducing the energy consumption of the pilot system. This energy-efficient configuration, however, had a small temperature difference between the hot feed and the coolant streams and therefore exhibited low water flux. Nevertheless, the low water flux of the pilot system was compensated by the large membrane surface area of the spiral-wound AGMD membrane modules. Equipped with a total membrane surface of 77.7 m2, the pilot AGMD process operated at the evaporator inlet and coolant inlet temperature of 70 ​°C and 25 ​°C respectively could produce 46 L ​h−1 of pure distillate that met the Vietnamese potable water standards. Particularly, the measured specific energy consumption of the pilot AGMD system was only 87 ​kWh.m−3, resulting in a production cost of 20.5 US$ per m3 of potable water.

Abstract Background The presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events. However, the mechanisms leading to IPH are not fully understood. The dominant view is that IPH is caused by leakage of erythrocytes from immature microvessels. The aim of the present study was to investigate whether there is an association between atherosclerotic plaque microvasculature and presence of IPH in a relatively large prospective cohort study of patients with symptomatic carotid plaque. Methods One hundred and thirty-two symptomatic patients with ≥2 mm carotid plaque underwent cardiovascular magnetic resonance (CMR) of the symptomatic carotid plaque for detection of IPH and dynamic contrast-enhanced (DCE)-CMR for assessment of plaque microvasculature. K trans, an indicator of microvascular flow, density and leakiness, was estimated using pharmacokinetic modelling in the vessel wall and adventitia. Statistical analysis was performed using an independent samples T-test and binary logistic regression, correcting for clinical risk factors. Results A decreased vessel wall K trans was found for IPH positive patients (0.051 ± 0.011 min− 1 versus 0.058 ± 0.017 min− 1, p = 0.001). No significant difference in adventitial K trans was found in patients with and without IPH (0.057 ± 0.012 min− 1 and 0.057 ± 0.018 min− 1, respectively). Histological analysis in a subgroup of patients that underwent carotid endarterectomy demonstrated no significant difference in relative microvessel density between plaques without IPH (n = 8) and plaques with IPH (n = 15) (0.000333 ± 0.0000707 vs. and 0.000289 ± 0.0000439, p = 0.585). Conclusions A reduced vessel wall K trans is found in the presence of IPH. Thus, we did not find a positive association between plaque microvasculature and IPH several weeks after a cerebrovascular event. Not only leaky plaque microvessels, but additional factors may contribute to IPH development. Trial registration NCT01208025. Registration date September 23, 2010. Retrospectively registered (first inclusion September 21, 2010). NCT01709045, date of registration October 17, 2012. Retrospectively registered (first inclusion August 23, 2011).

Behaviors, traits and characteristics are transmitted from parents to offspring because of complex genetic and non-genetic processes. We review genetic and non-genetic mechanisms of intergenerational transmission of psychopathology and parenting and focus on recent methodological advances in disentangling genetic and non-genetic factors. In light of this review, we propose that future studies on intergenerational transmission should aim to disentangle genetic and non-genetic transmission, take a long-term longitudinal perspective, and focus on paternal and maternal intergenerational transmission. We present four large longitudinal cohort studies within the Consortium on Individual Development, which together address many of these methodological challenges. These four cohort studies aim to examine the extent to which genetic and non-genetic transmission from the parental generation shapes parenting behavior and psychopathology in the next generation, as well as the extent to which self-regulation and social competence mediate this transmission. Conjointly, these four cohorts provide a comprehensive approach to the study of intergenerational transmission.

Summary: Somitogenesis, the primary segmentation of the vertebrate embryo, is associated with oscillating genes that interact with a wave of cell differentiation. The necessity of cell-matrix adherence and embryonic tension, however, suggests that mechanical cues are also involved. To explicitly investigate this, we applied surplus axial strain to live chick embryos. Despite substantial deformations, the embryos developed normally and somite formation rate was unaffected. Surprisingly, however, we observed slow cellular reorganizations of the most elongated somites into two or more well-shaped daughter somites. In what appeared to be a regular process of boundary formation, somites divided and fibronectin was deposited in between. Cell counts and morphology indicated that cells from the somitocoel underwent mesenchymal-epithelial transition; this was supported by a Cellular Potts model of somite division. Thus, although somitogenesis appeared to be extremely robust, we observed new boundary formation in existing somites and conclude that mechanical strain can be morphologically instructive. : Poultry Embryology; Mechanical Modeling; Developmental Biology Subject Areas: Poultry Embryology, Mechanical Modeling, Developmental Biology

Background: The aim of A MAastricht Contrast-Induced Nephropathy Guideline (AMACING) trial was to evaluate non-inferiority of no prophylaxis compared to guideline-recommended prophylaxis in preventing contrast induced nephropathy (CIN), and to explore the effect on long-term post-contrast adverse outcomes. The current paper presents the long-term results. Methods: AMACING is a single-centre, randomised, parallel-group, open-label, phase 3, non-inferiority trial in patients with estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2 combined with risk factors, undergoing elective procedures requiring intravenous or intra-arterial iodinated contrast material. Exclusion criteria were eGFR

Objective: Deep venous obstruction (DVO) is a great burden on the healthcare system and patients' quality of life (QoL). Case series show stenting is safe and effective, however most studies lack control groups and QoL changes have not been compared with conventional treatment. The aim was to assess the difference in QoL changes from baseline to 12 months between stent and conventionally treated patients with DVO., Methods: Subjects > 18 years old with DVO due to post-thrombotic (PTS) or non-thrombotic iliac vein lesions (NIVLs) in a tertiary hospital were prospectively randomised to best medical therapy (BMT) or stent placement with BMT in a ratio 2:1, stratified for PTS or NIVL. The primary outcome was the between group difference in VEINES-QoL scores change from baseline to 12 months after treatment. Secondary outcomes included the difference in score changes for EuroQoL 5-Dimension 5 Level (EQ-5D-5L), Pain Disability Index (PDI), Venous Clinical Severity Score (VCSS), and the Villalta score., Results: After three years, the inclusion rate dropped to almost zero, therefore the study had to be stopped. Sixty-three patients were randomised to either the stent (n = 42) or control group (n = 21). Overall, 50 patients had available data for primary outcome analysis. The adjusted mean difference between 12 month scores for VEINES-QoL and VEINES-Sym was 8.07 (95% CI 3.04 - 13.09) and 5.99 (95% CI 0.75 - 11.24) (p = .026), respectively, in favour of the stent group. The differences were significant, but a pre-defined meaningful 14 point improvement in QoL was not reached. The mean difference between 12 month scores for VCSS was -2.93 (95% CI -5.71 - 0.16, p = .040), -11.83 (95% CI -20.81 - 2.86, p = .011) for PDI, 0.015 (95% CI -0.12 - 0.15, p = .82) for the EQ-5D index, and -2.99 (95% CI -7.28 - 1.30, p = .17) for the Villalta score., Conclusion: Symptomatic patients with DVO who received dedicated venous stents had significantly higher VEINES-QoL/Sym scores at 12 months compared with the control group, but the between group difference was lower than the pre-specified clinically relevant QoL difference of at least 14 points., Study Registration Number: NCT03026049., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Imaging findings can be affected by histopathological characteristics, such as breast cancer subtypes. The aim was to determine whether the diagnostic performance, in particular negative predictive value (NPV), of axillary US differs per subtype of breast cancer., Methods: All patients diagnosed between 2008 and 2016 in our hospital with primary invasive breast cancer and an axillary US prior to axillary surgery were included. Histopathology of axillary surgery specimens served as gold standard. The NPV, sensitivity, specificity, positive predictive value (PPV) and accuracy of the axillary US were determined for the overall population and for each subtype (ER+/PR+HER2-,HER2+, triple negative tumors). The Chi-square test was used to determine the difference in diagnostic performance parameters between the subtypes., Results: A total of 1094 breast cancer patients were included. Of these, 35 were diagnosed with bilateral breast cancer, resulting in 1129 cancer cases. Most common subtype was ER+/PR+HER2- in 858 cases (76.0%), followed by 150 cases of HER2+ tumors (13.3%) and 121 cases of triple negative tumors (10.7%). Sensitivity, specificity and accuracy of axillary US did not significantly differ between the subtypes. There was a significant difference for NPV between triple negative tumors and HER2+ tumors (90.3% vs. 80.2%, p = 0.05) and between HER2+ and ER/PR+HER2- tumors (80.2% vs. 87.2%, p = 0.04)., Conclusion: There was no significant difference in the diagnostic performance of axillary US between the subtypes, except for NPV. This was highest in triple negative subtype and lowest in HER2+ tumors. This can be explained by the difference in prevalence of axillary lymph node metastases in our cohort., (Copyright © 2019. Published by Elsevier Ltd.)

Unlabelled: Essentials Little is known about the hemodynamic consequences of deep venous obstructive disease. We investigated pressure changes in 22 patients with unilateral postthrombotic obstruction. Common femoral vein pressure significantly increased after walking, compared to control limbs. Common femoral vein hypertension could explain the debilitating effect of venous claudication. Click to hear Dr Ten Cate's perspective on postthrombotic syndrome, Summary: Background Little is known about the hemodynamic consequences of deep venous obstructive disease. Objectives The aim of this study was to investigate the hemodynamic effect of postthrombotic obstruction of the iliofemoral veins and to determine what pressure parameters differentiate best between limbs with post-thrombotic obstructive disease of the iliofemoral veins and those without obstruction. Methods Twenty-two participants with unilateral obstruction of the iliac and common femoral veins underwent a standardized treadmill test with simultaneous bilateral invasive pressure measurements in the common femoral vein and dorsal foot vein. Results Mean age was 42.8 ± 11.9 years and 86.4% of participants were female. Postthrombotic limbs showed a mean common femoral vein (CFV) pressure increase of 28.1 ± 21.0 mmHg after walking, compared with 2.1 ± 6.2 mmHg in control limbs (26.0 mmHg difference; 95% confidence interval [CI], 17.1-34.9). Less difference was observed in the dorsal foot vein (net drop of 36.8 ± 22.7 mmHg in affected limbs vs. 48.7 ± 23.1 mmHg in non-affected limbs, 11.9 mmHg difference; 95% CI, -1.3 to 25.0). Change in CFV pressure after walking yielded the best discrimination between affected and non-affected limbs (area under the receiver operated characteristic curve of 0.94 [95% CI, 0.85-1.00], compared with 0.57 [95% CI, 0.37-0.76] in the dorsal foot vein, P < 0.001). Conclusions Common femoral vein pressure significantly increases during ambulation in patients with iliofemoral postthrombotic obstruction, which could explain the debilitating effects of venous claudication. This is an indication that patients with an iliofemoral obstruction may benefit from further treatment that resolves the deep vein obstruction., Clinical Trial Registration: https://clinicaltrials.gov/show/NCT01846780., (© 2016 International Society on Thrombosis and Haemostasis.)

Purpose: To provide a systematic review and meta-analysis of studies investigating sentinel lymph node biopsy after neoadjuvant systemic therapy in pathologically confirmed node positive breast cancer patients., Methods: Pubmed and Embase databases were searched until June 19th, 2015. All abstracts were read and data extraction was performed by two independent readers. A random-effects model was used to pool the proportion for identification rate, false-negative rate (FNR) and axillary pCR with 95% confidence intervals. Subgroup analyses affirmed potential confounders for identification rate and FNR., Results: A total of 997 abstracts were identified and eventually eight studies were included. Pooled estimates were 92.3% (90.8-93.7%) for identification rate, 15.1% (12.7-17.6%) for FNR and 36.8% (34.2-39.5%) for axillary pCR. After subgroup analysis, FNR is significantly worse if one sentinel node was removed compared to two or more sentinel nodes (23.9% versus 10.4%, p = 0.026) and if studies contained clinically nodal stage 1-3, compared to studies with clinically nodal stage 1-2 patients (21.4 versus 13.1%, p = 0.049). Other factors, including single tracer mapping and the definition of axillary pCR, were not significantly different., Conclusion: Based on current evidence it seems not justified to omit further axillary treatment in every clinically node positive breast cancer patients with a negative sentinel lymph node biopsy after neoadjuvant systemic therapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To determine the best location to measure the arterial peak flow (APF) in patients with peripheral arterial disease in order to facilitate clinical standardization., Methods: Two hundred and fifty-nine patients with varying degrees of peripheral artery disease (PAD) and 48 patients without PAD were included. All patients underwent magnetic resonance phase-contrast imaging of the common femoral artery (CFA), superficial femoral artery (SFA), and popliteal artery (PA). APF values of patients with PAD were compared with patients with no PAD. The discriminative ability to identify PAD was evaluated by means of receiver-operator characteristic curves and the corresponding areas under the curve (AUC)., Results: Mean APF values in patients with PAD were reduced by 42%, 55% and 59% compared with non-PAD patients for the CFA, SFA, and PA, respectively (p < .01). The AUC's were 0.84, 0.92, and 0.93 for the CFA, SFA, and PA, respectively., Conclusion: The APF measured at the level of the PA shows the largest differences between patients with PAD and patients with no PAD and the best discriminative ability compared with the APF acquired in the CFA or SFA. The PA seems to be the most suitable level for standardized flow measurements in patients with PAD in order to obtain relevant functional information about the vascular status., (Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Establishing inflammatory activity in sarcoidosis patients with persistent disabling symptoms is important. Whole body F(18)-FDG PET/CT (PET) appeared to be a sensitive method to detect inflammatory activity in newly diagnosed symptomatic sarcoidosis. The aim was to assess the presence of inflammatory activity using PET in sarcoidosis patients with unexplained persistent disabling symptoms and the association between PET findings and serological inflammatory markers., Methods: Sarcoidosis patients who underwent a PET between June 2005 and June 2010 (n = 89), were retrospectively included. All PET scans were examined and positive findings were classified as thoracic and/or extrathoracic. As serological markers of inflammatory activity angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), and neopterin were considered., Results: In 65/89 (73%) of the studied patients PET was positive, 52 of them (80%) had serological signs of inflammatory activity. In 14/15 patients with a Chest X-ray stage IV PET was positive. In 80% of the PET positive patients extrathoracic inflammatory activity was found. Sensitivity of combined serological inflammatory markers for the presence of inflammatory activity as detected by PET was 80%, specificity 100%, positive predictive value 100%, negative predictive value 65%., Conclusions: The majority of sarcoidosis patients with persistent disabling symptoms, even those with radiological stage IV, had PET positive findings with remarkably 80% extrathoracic lesions. In 20% PET was positive without signs of serological inflammatory activity. PET appeared to be of additional value to assess inflammatory activity in patients with persistent symptoms in the absence of signs of serological inflammatory activity and to detect extrathoracic lesions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: This article investigates whether differences in utility scores based on the EQ-5D and the SF-6D have impact on the incremental cost-utility ratios in five distinct patient groups., Methods: We used five empirical data sets of trial-based cost-utility studies that included patients with different disease conditions and severity (musculoskeletal disease, cardiovascular pulmonary disease, and psychological disorders) to calculate differences in quality-adjusted life-years (QALYs) based on EQ-5D and SF-6D utility scores. We compared incremental QALYs, incremental cost-utility ratios, and the probability that the incremental cost-utility ratio was acceptable within and across the data sets., Results: We observed small differences in incremental QALYs, but large differences in the incremental cost-utility ratios and in the probability that these ratios were acceptable at a given threshold, in the majority of the presented cost-utility analyses. More specifically, in the patient groups with relatively mild health conditions the probability of acceptance of the incremental cost-utility ratio was considerably larger when using the EQ-5D to estimate utility. While in the patient groups with worse health conditions the probability of acceptance of the incremental cost-utility ratio was considerably larger when using the SF-6D to estimate utility., Conclusions: Much of the appeal in using QALYs as measure of effectiveness in economic evaluations is in the comparability across conditions and interventions. The incomparability of the results of cost-utility analyses using different instruments to estimate a single index value for health severely undermines this aspect and reduces the credibility of the use of incremental cost-utility ratios for decision-making.

Radiologists may be relieved from work that could be performed by radiographers. This systematic literature review focuses on the performance of radiographers (also referring to technologists and physician assistants) compared with radiologists in the interpretation of mammograms; the effect of training; and the question whether there are any studies evaluating the effects of involving radiographers in the interpretation of diagnostic mammograms in daily clinical practice on the sensitivity and specificity of cancer detection in breast imaging. Six studies met the inclusion criteria (primary aim of the study has to be the evaluation of the performance of radiographers, sensitivity and specificity have to be reported or calculable and there has to be a sufficient gold standard). The results showed that, in a screening setting, radiographers scored higher false positive rates with a similar sensitivity in the detection of malignancies, compared with radiologists. Furthermore, results suggested that training could improve their performance. No studies were reported assessing the performance of radiographers interpreting diagnostic mammograms in a consecutive patient population in a daily clinical setting. This indicates a need for a well-designed diagnostic study using an adequate gold standard, in order to evaluate the feasibility of deploying radiographers in the interpretation of diagnostic mammograms in a clinical setting.

Objectives: (1) To help identify patients with poor adherence and (2) to identify potential reasons that impede or facilitate adherence., Methods: Seventeen patients who used antihypertensive drugs participated in semi-standardized interviews. Interviews were recorded and reviewed by two investigators. Forty-four items were selected. An exploratory factor analysis was performed. Convergent validity was assessed by evaluating the association between sum scores on the identified subscales and three other adherence measures: (1) the Brief Medication Questionnaire (BMQ), (2) pharmacy refill records and (3) electronic monitoring. Regression analysis was used to evaluate the magnitude of associations., Results: Two hundred and fifty-five (90%) patients completed the questionnaire. Factor analysis resulted in a four-factor solution, explaining 30% of cumulative variance among respondents. The factors (scales) were labeled: positive attitude towards health care and medication (I), lack of discipline (II), aversion towards medication (III) and active coping with health problems (IV). Chronbach's alpha coefficient was 0.75, 0.80, 0.63 and 0.76 for scales I, II, III and IV, respectively. Convergent validity was partly supported by statistically significant associations that were found between sum scores of subscales 1 and II and the BMQ and electronic monitoring, respectively., Conclusion: The MUAH-questionnaire has excellent psychometric properties and may be useful to identify factors that impede or facilitate adherence. However, it is not clear to what extent the questionnaire measures actual adherence., Practice Implications: Validation of the MUAH-questionnaire in other studies is needed.

Background: Current treatment modalities for chronic leg ulcers are time consuming, expensive, and only moderately successful. Recent data suggest that creating a subatmospheric pressure by vacuum-assisted closure (V.A.C., KCI Concepts, San Antonio, Texas) therapy supports the wound healing process., Methods: The efficacy of vacuum-assisted closure in the treatment of chronic leg ulcers was prospectively studied in a randomized controlled trial in which 60 hospitalized patients with chronic leg ulcers were randomly assigned to either treatment by V.A.C. or therapy with conventional wound care techniques. The primary outcome measure was the time to complete healing (days). Statistical analysis was performed on the intention-to-treat basis., Results: The median time to complete healing was 29 days (95% confidence interval [CI], 25.5 to 32.5) in the V.A.C. group compared with 45 days (95% CI, 36.2 to 53.8) in the control group (P = .0001). Further, wound bed preparation during V.A.C. therapy was also significantly shorter at 7 days (95% CI 5.7 to 8.3) than during conventional wound care at 17 days (95% CI, 10 to 24, P = .005). The costs of conventional wound care were higher than those of V.A.C. Both groups showed a significant increase in quality of life at the end of therapy and a significant decrease in pain scores at the end of follow-up., Conclusions: V.A.C. therapy should be considered as the treatment of choice for chronic leg ulcers owing to its significant advantages in the time to complete healing and wound bed preparation time compared with conventional wound care. Particularly during the preparation stage, V.A.C. therapy appears to be superior to conventional wound care techniques.

Incidence of atherosclerosis and atherosclerosis-related complications will increase significantly in the coming decennia. Research identified many serum and plasma markers that are associated with cardiovascular disease. However, little is known about the prognostic value of these markers to identify patients at risk for future cardiovascular events. Therefore, we aimed to investigate the prognostic value of three of these markers (soluble CD40 ligand (sCD40L), interleukin-6 (IL-6) and oxidized low-density lipoprotein (oxLDL)) with respect to coronary vascular disease and stroke. For this reason the Medline database was searched for the period January 1999-January 2005. To be selected in our study, concentration of the marker had to be determined at baseline, follow-up period had to be longer than 3 months and an estimate of relative risk had to be available. Based on these criteria, 4 studies for sCD40L, 10 for IL-6 and 2 for oxLDL were selected. Relative risk estimates adjusted for potential confounders varied between 1.9 and 2.8 for sCD40L, between 1.1 and 3.1 for IL-6 and between 1.9 and 3.2 for oxLDL. In conclusion, this systematic review shows that sCD40L, IL-6 and oxLDL are associated with an increased relative risk of developing cardiovascular disease.

Objective: Methodological standards for clinical pharmacogenetic studies should be developed to improve reporting of studies and facilitate their inclusion in systematic reviews. The essence of these studies lies within the concept of effect modification., Study Design and Setting: A narrative review discussing methodological issues in the design and reporting of pharmacogenetic studies., Results: Studying effect modification within a trial leads to the comparison of subgroups based on genotype. Differences in effect based on genotype should preferably be expressed in absolute terms (risk differences) to facilitate clinical decisions on treatment. Information on the distribution of potential effect modifiers or prognostic factors should be available to prevent a biased comparison of differences in effect between genotypes. The distribution of genotypes should also be presented and compared to Hardy-Weinberg equilibrium to check for selection bias. Additional points of interest include the possibility of selective nonavailability of biomaterial and the choice of a statistical model to study effect modification., Conclusion: Additional methodological issues should be taken into account when designing and reporting pharmacogenetic studies, to ensure high study quality. We present several important issues for future studies investigating drug-gene interactions that can serve as a basis for further discussion on methodology in pharmacogenetics.

Objective: Incorrect and unnecessary antibiotic prescribing enhancing bacterial resistance rates might be reduced if viral and bacterial lower respiratory tract infections (LRTI) could be differentiated clinically. Whether this is possible is often doubted but has rarely been studied in general practice., Study Design and Setting: This was an observational cohort study in 15 general practice surgeries in the Netherlands., Results: Etiologic diagnoses were obtained in 112 of 234 patients with complete data (48%). Viral pathogens were found as often as bacterial pathogens. Haemophilus (para-) influenzae was most frequently found. None of the symptoms and signs correlated statistically significantly with viral or bacterial LRTI. Erythrocyte sedimentation rate >50 (odds ratio [OR] 2.3-3.3) and C-reactive protein (CRP) >20 (OR 2.1-4.6) were independent predictors for viral LRTI and bacterial LRTI when compared with microbiologically unexplained LRTI., Conclusion: Extensive history-taking and physical examination did not provide items that predict viral or bacterial LRTI in adult patients in daily general practice. We could not confirm CRP to differentiate between viral and bacterial LRTI.

Case control studies on the association between sunlight exposure and melanoma risk show considerable differences in design; this could be responsible for the variation in study results. In an attempt to resolve the controversy between study results, the results of 25 publications on case control studies were evaluated using meta-analytical techniques. Comparison of odds ratios between subgroups of studies revealed that the range of odds ratios was far greater for hospital-based studies than for population-based studies. For the latter type of studies, the odds ratios were homogeneous and the pooled odds ratios were 1.57 (95% confidence interval [CI], 1.29-1.91) for intermittent sunlight exposure and 0.73 (95% CI, 0.60-0.89) for chronic exposure. However, among other problems, the lack of standardized measures for sunlight exposure warrants cautious interpretation of these results. It is concluded that evidence to support the intermittent sunlight theory is still far from complete.