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Adequate and transparent reporting is necessary for critically appraising research. Yet, evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-empaneled a group of authors to develop methodological and statistical reporting guidelines identifying the minimum information needed to document and evaluate observational studies and clinical trials in oral health: the OHstat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The final version was subsequently approved by the Task Force in September 2021, submitted for journal review in 2022, and revised in 2023. The checklist consists of 48 guidelines: 5 for introductory information, 17 for methods, 13 for statistical analysis, 6 for results, and 7 for interpretation; 7 are specific to clinical trials. Each of these guidelines identifies relevant information, explains its importance, and often describes best practices. The checklist was published in multiple journals. The article was published simultaneously in JDR Clinical and Translational Research, the Journal of the American Dental Association, and the Journal of Oral and Maxillofacial Surgery. Completed checklists should accompany manuscripts submitted for publication to these and other oral health journals to help authors, journal editors, and reviewers verify that the manuscript provides the information necessary to adequately document and evaluate the research., (Copyright © 2024 Task Force on Design & Analysis in Oral Health Research 2024. Published by Elsevier Inc. All rights reserved.)

Adequate and transparent reporting is necessary for critically appraising published research. Yet, ample evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-identified the minimum information needed to report and evaluate observational studies and clinical trials in oral health: the OHStat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The guidelines were subsequently revised by the Task Force's writing group. The guidelines draw heavily from the Consolidated Standards for Reporting Trials (CONSORT), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and CONSORT harms guidelines and incorporate the SAMPL guidelines for reporting statistics, the CLIP principles for documenting images, and the GRADE indicating the quality of evidence. The guidelines also recommend reporting estimates in clinically meaningful units using confidence intervals, rather than relying on P values. In addition, OHStat introduces 7 new guidelines that concern the text itself, such as checking the congruence between abstract and text, structuring the discussion, and listing conclusions to make them more specific. OHStat does not replace other reporting guidelines; it incorporates those most relevant to dental research into a single document. Manuscripts using the OHStat guidelines will provide more information specific to oral health research., (Copyright © 2024 Task Force on Design & Analysis in Oral Health Research 2024. Published by Elsevier Inc. All rights reserved.)

Prolonged grief disorder, characterized by severe, persistent and disabling grief, has recently been added to the DSM-5-TR and ICD-11. Treatment for prolonged grief symptoms shows limited effectiveness. It has been suggested that prolonged grief symptoms exacerbate insomnia symptoms, whereas insomnia symptoms, in turn, may fuel prolonged grief symptoms. To help clarify if treating sleep disturbances may be a viable treatment option for prolonged grief disorder, we examined the proposed reciprocal relationship between symptoms of prolonged grief and insomnia. On three time points across 6-month intervals, 343 bereaved adults (88% female) completed questionnaires to assess prolonged grief, depression, and insomnia symptoms. We applied random intercept cross-lagged panel models (RICLPMs) to assess reciprocal within-person effects between prolonged grief and insomnia symptoms and, as a secondary aim, between depression and insomnia symptoms. Changes in insomnia symptoms predicted changes in prolonged grief symptoms but not vice versa. Additionally, changes in depression and insomnia symptoms showed a reciprocal relationship. Our results suggest that targeting insomnia symptoms after bereavement is a viable option for improving current treatments for prolonged grief disorder., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Navigating the complexities of a severe burn injury is a challenging endeavour where the natural course of some patients can be difficult to predict. Straddling both the coagulation and inflammatory cascades that feature strongly in the burns systemic pathophysiology, we propose the pleiotropic protein C (PC) system may produce a viable biomarker to assist traditional evaluation methods for diagnostic and prognostic purposes., Methods: We enrolled 86 patients in a prospective observational cohort study. Over three weeks, serial blood samples were taken and measured for PC, activated (A)PC, their receptor endothelial protein C receptor (EPCR), and a panel of inflammatory cytokines including C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and IL-17. Their temporal trends were analysed alongside clinical factors including burn size, burn depth, presence of inhalational injury, and a composite outcome of requiring increased support., Results: (i) APC increased from a nadir on Day 3 (2.3±2.1ng/mL vs 4.1±2.5ng/mL by Day 18, p<0.0005), only becoming appropriately correlated to PC from Day 6 onwards (r=0.412-0.721, p<0.05 for all Days 6-21). (ii) This early disturbance in the PC system was amplified in the more severe burns (≥30% total body surface area, predominantly full thickness, or with inhalational injury), which were characterised by a marked fall in PC activation (approximated by APC/PC ratio) and APC levels during Days 0-3 with low unchanged PC levels. Critically low levels of this cytoprotective agent was associated with greater inflammatory burden, as reflected by significantly elevated CRP, IL-6, and IL-8 levels in the more severe compared to less severe burns, and by negative correlations between both PC and APC with most inflammatory cytokines. (iii) Alongside clinical markers of severity at admission (burn size, burn depth, and presence of inhalational injury), only Day 0 APC/PC ratio (OR 1.048 (1.014-1.083), p=0.006), APC (OR 1.364 (1.032-1.803), p=0.029), PC (OR 0.899 (0.849-0.953), p<0.0005), and not any inflammatory cytokines were predictive markers of requiring increased support. Uniquely, decreased Day 0 PC was further individually associated with each increased total length of stay, ICU length of stay, intravenous fluid resuscitation, and total surgeries, as well as possibly mortality., Conclusion: An early functional depletion of the cytoprotective PC system provides a physiological link between severe burns and the cytokine storm, likely contributing to worse outcomes. Our findings on the changes in APC, PC and PC activation during this pathological state support APC and PC as early diagnostic and prognostic biomarkers, and provides a basis for their therapeutic potential in severe burn injuries., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Background: Acute abdominal aortic occlusion (AAO) is a rare vascular emergency associated with high morbidity and mortality. In the present study, we analyzed the clinical management and outcomes for a consecutive patient series during a 16-year period., Methods: We included all patients with an acute AAO and bilateral acute limb ischemia who had been treated between 2004 and 2019. Patients with dissection, aneurysm rupture, or chronic occlusive disease were excluded. The patient characteristics, surgical procedures, and outcomes were extracted retrospectively from a prospective aortic database, electronic patient files, and outpatient examination records. The extent of ischemia was classified according to the TASC II (Inter-Society Consensus for the Management of Peripheral Arterial Disease) section on acute limb ischemia. The primary endpoints were 30-day mortality (safety endpoint) and the combined 6-month amputation and/or death rate (efficacy endpoint). The follow-up outcomes, amputation rates, and 30-day complications were evaluated as secondary endpoints. The patient cohort was divided into four 4-year groups (2004-2007, 2008-2011, 2012-2015, 2016-2019) to assess the outcome changes over time. Statistical analysis included χ 2 tests and univariate and linear regression analyses., Results: A total of 74 patients (57% male; median age, 64.5 years) with an acute AAO were identified. Arterial thrombosis was the most common etiology (66%). The extent of ischemia was TASC I, IIa, IIb, and III in 7%, 39%, 40%, and 14%, respectively. The patient numbers had increased significantly over time (P = .016). Of the patients, 42% had undergone open transfemoral recanalization (including hybrid procedures), 35% open aortic surgery, 15% extra-anatomic bypass surgery, and 5% (four patients) endovascular therapy alone. The overall 30-day mortality rate was 23%, and the 6-month amputation and/or death rate was 43%. The 30-day mortality rate had declined significantly from 54% for 2004 to 2007 to 10% for 2011 to 2015 (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.001-0.52) and 20% for 2016 to 2019 (OR, 0.21; 95% CI, 0.05-0.90), a statistically nonsignificant trend showing that the relative decline in the use of open aortic procedures was associated with decreased 30-day mortality (P = .06). Univariate analysis indicated that elevated serum lactate on admission (OR, 3.33; 95% CI, 1.06-10.48) and an advanced stage of limb ischemia (OR, 4.33), were strongly associated with an increased 30-day mortality rate. The incidence of severe postoperative systemic complications also indicated a greater incidence of both primary endpoints. The 6-month amputation and/or mortality rates were also affected by the presence of atrial fibrillation (OR, 3.63; 95% CI, 1.34-9.79) and increased patient age (OR, 3.96; 95% CI, 1.49-10.53)., Conclusions: Acute AAO remains a life-threatening emergency. Immediate transfemoral open or endovascular techniques should be preferred, if technically possible and proper intraoperative imaging is available., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy., Competing Interests: Conflict of Interest AR reports speaker honoraria and advisory board honoraria from Janssen, Servier, Medice, Shire and neuraxpharm. VA has received compensations for his contributions as member of advisory boards and for presentations for the following companies: Astra-Zeneca, Eli Lilly, Janssen-Cilag, Lundbeck, Otsuka, Sanofi, Servier, and Trommsdorff. TCE is part funded by a program grant from the UK Medical Research Council (MR/M021475/1), and the National Institute for Health Research (NIHR) Biomedical Research center at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. PP reports having received research funding from Volkswagenstiftung (A124277) and that he is shareholder of a commercial company (VTplus) that develops virtual reality research systems. KD is a member of the Janssen Pharmaceuticals, Inc. Steering Committee Neurosciences. All other authors reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Recently, sea-dumped chemical weapons (CWs) containing toxic chemical warfare agents (CWAs) have raised international attention. It is well known that CWAs are leaking from corroded munitions causing a risk to the surrounding marine environment, while the impact on marine biota is still unknown. In this study, cod (Gadus morhua) was used as a model species to study the possible bioaccumulation of phenylarsenic CWAs and their negative effects at multiple levels of biological organization on fish living in the vicinity of a major CWs dumpsite in the Bornholm Basin in the Baltic Sea. In total, 14% of the cod muscle samples collected close to the main dumpsite contained trace levels of phenylarsenic CWAs. However, most of the biomarkers measured did not show clear differences between this area compared with a lesser contaminated reference area. On the other hand, significant changes in some biomarkers were observed in individuals containing trace levels of CWA-related chemicals. The results gained in this study have significant importance for environmental risk assessment and for evaluating the risk of CWA contamination for human seafood consumers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Large quantities of chemical warfare agents (CWAs), such as phenylarsenic chemicals, were disposed by sea-dumping after World War II. Nowadays, the release of these toxic chemicals from munitions poses a potential threat to living organisms. This study investigates the fate of these chemicals in fish by exposing selected CWA-related phenylarsenic chemicals and their oxidation products to cod (Gadus morhua) liver S9 fraction in vitro. Clark I (DA), Adamsite (DM) and their corresponding oxidation products as well as triphenylarsine oxide (TPA[ox]) and phenylarsonic acid (PDCA[ox]) were used as chemicals in in vitro experiments. Glutathione (GSH) conjugates of DA, DM and PDCA-related chemicals were found to be the most dominant metabolites, and methylated metabolites were detected as well, suggesting that these compounds are metabolised in the presence of cod liver enzymes. TPA[ox] was the only compound tested that did not form a GSH conjugate or methylated metabolite, indicating a different biotransformation pathway for this compound. Furthermore, hydroxylated metabolites were detected for each tested chemical. Due to their reactive nature, GSH conjugates may be difficult to detect in fish samples from CWA dumpsites. In contrast, both methylated and hydroxylated metabolites of phenylarsenic chemicals are promising target chemicals for the detection of CWA-related contamination in fish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Corrosion and disintegration of munition shells from the World Wars increase the risk that explosives are released into the marine environment, exposing a variety of organisms. Only few studies investigated contamination of fish with explosives in the field under environmental conditions. Here we present a comprehensive study on the contamination status of dab (Limanda limanda) from a munition dumpsite and from reference sites in the Baltic Sea. Bile of 236 dab from four different study sites, including a dumpsite for conventional munitions, was investigated and explosive compounds were detected by high performance liquid chromatography-mass spectrometry. Five explosive compounds were identified, including 2,4,6-trinitrotoluene, 4-amino-2,6-dinitrolouene, and hexahydro-1,3,5-trinitro-1,3,5-triazine. 48% of the samples from the dumpsite contained at least one explosive compound. The results prove that toxic explosive compounds from a dumpsite in the Baltic Sea are accumulated by flatfish and may therefore pose a risk to fish health and human food safety., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Protein C circulates in human plasma to regulate inflammation and coagulation. It has shown a crucial role in wound healing in animals, and low plasma levels predict the presence of a wound in diabetic patients. However, no detailed study has measured protein C levels in patients with severe burns over the course of a hospital admission. A severe burn is associated with dysfunction of inflammation and coagulation as well as a significant risk of morbidity and mortality. The current methods of burn assessment have shortcomings in reliability and have limited prognostic value. The discovery of a biomarker that estimates burn severity and predicts clinical events with greater accuracy than current methods may improve management, resource allocation and patient counseling. This is the first study to assess the potential role of protein C as a biomarker of burn severity. We measured the plasma protein C levels of 86 patients immediately following a severe burn, then every three days over the first three weeks of a hospital admission. We also analysed the relationships between burn characteristics, blood test results including plasma protein C levels and clinical events. We used a primary composite outcome of increased support utilisation defined as: a mean intravenous fluid administration volume of five litres or more per day over the first 72 h of admission, a length of stay in the intensive care unit of more than four days, or greater than four surgical procedures during admission. The hypothesis was that low protein C levels would be negatively associated with increased support utilisation. At presentation to hospital after a severe burn, the mean plasma protein C level was 76 ± 20% with a range of 34-130% compared to the normal range of 70-180%. The initial low can be plausibly explained by impaired synthesis, increased degradation and excessive consumption of protein C following a burn. Levels increased gradually over six days then remained at a steady-state until the end of the inpatient study period, day 21. A multivariable regression model (Nagelkerke's R 2  = 0.83) showed that the plasma protein C level on admission contributed the most to the ability of the model to predict increased support utilisation (OR = 0.825 (95% CI = 0.698-0.977), P = 0.025), followed by burn size (OR = 1.252 (95% CI = 1.025-1.530), P = 0.027), burn depth (partial thickness was used as the reference, full thickness OR = 80.499 (1.569-4129.248), P = 0.029), and neutrophil count on admission (OR = 1.532 (95% CI = 0.950-2.473), P = 0.08). Together, these four variables predicted increased support utilisation with 93.2% accuracy, 83.3% sensitivity and 97.6% specificity. However if protein C values were disregarded, only 49.5% of the variance was explained, with 82% accuracy, 63% sensitivity and 91.5% specificity. Thus, protein C may be a useful biomarker of burn severity and study replication will enable validation of these novel findings., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

The gene coding for glycine receptor β subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk») in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass., Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci., Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms)., Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection., Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

The Baltic Sea is a severely disturbed marine ecosystem that has previously been used as a dumping ground for Chemical Warfare Agents (CW). The presence of unexploded underwater ordnance is an additional risk factor for offshore activities and an environmental risk for the natural resources of the sea. In this paper, the focus is on descriptions of the marine habitat based on the observations arising from studies linked to the CHEMSEA, MODUM and DAIMON projects. Investigated areas of Bornholm, Gotland and Gdańsk Deeps are similarly affected by the Baltic Sea eutrophication, however, at depths greater than 70m several differences in local hydrological regimes and pore-water heavy metal concentrations between those basins were observed. During the lifespan of presented studies, we were able to observe the effects of Major Baltic Inflow, that started in December 2014, on local biota and their habitats, especially in the Bornholm Deep area. Reappearance of several meiofauna taxa and one macrofauna specimen was observed approximately one year after this phenomenon, however it's ecological effects already disappeared in March 2017. According to our findings and to the EUNIS Habitat Classification, the three reviewed areas should be characterized as Deep Sea Muddy Sands, while the presence of suspicious bomb-like objects both beneath and on top of the sediments confirms their CW dumpsite status., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Litter is present in all marine waters around the globe. It consists of several compound classes of which plastic is of special interest because of its high abundance and possible threat to marine organisms. The regional distribution, composition and abundance of large litter items (LI) at the sea floor of the North Sea and the Baltic Sea were investigated based on 175 bottom trawls between 2013 and 2015. Different types of marine litter >2.5cm were classified according to the protocol of the ICES International Bottom Trawl Survey. The results showed considerable geographical variation: In the North Sea, a mean litter abundance of 16.8LI/km 2 was found, whereas the litter abundance in the Baltic Sea was significantly lower (5.07LI/km 2 ). In general, plastic represented 80% of the litter items. During the study, some methodical aspects with possible impact on the results were identified that need to be addressed in future sampling campaigns., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In the framework of the ICON project (Integrated Assessment of Contaminant Impacts on the North Sea), common dab (Limanda limanda) from seven offshore sampling areas in the North Sea, Icelandic waters and the western Baltic Sea were examined in 2008 for the presence of externally visible diseases and parasites (EVD), macroscopic liver neoplasms (tumours) (MLN) and histopathological liver lesions (LH). Methodologies applied followed standardised ICES and BEQUALM protocols. The EDV results revealed pronounced spatial variation, with dab from the central and northern North Sea sampling areas showing the highest disease prevalence. MLN were recorded only in North Sea dab from the German Bight, Firth of Forth and Ekofisk at a low prevalence. LH results revealed a dominant prevalence of non-specific, mostly inflammatory, lesions and a low prevalence of early toxicopathic non-neoplastic lesions, tumour pre-stages (foci of cellular alteration) and liver tumours. For the analysis and assessment of spatial variation of EVD, a Fish Disease Index (FDI) was calculated for individual dab, summarising data on the presence/absence of EDV, their severity grades, effects on the host and compensating for effects of length, sex and season. FDI data confirmed that the health status of North Sea dab from the offshore areas Dogger Bank, Ekofisk and Firth of Forth was significantly worse than in dab from the German Bight, Icelandic areas and the western Baltic Sea. An assessment of the disease data following ICES/OSPAR criteria was accomplished by applying established numeric background (BAC) and ecological assessment criteria (EAC) for EDV, MLN and LH. The combined assessment of the three disease categories indicated that health effects classified as unacceptable were rare and mainly affected dab from the North Sea. Based on the findings of the present study, it is recommended to monitor wild fish diseases in the context of assessing the impact of hazardous substances and other stressors on the marine environment. The Fish Disease Index (FDI) is regarded as a strong tool for disease data analysis and assessment, suitable as ecosystem health indicator., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Many maritime countries in Europe have implemented marine environmental monitoring programmes which include the measurement of chemical contaminants and related biological effects. How best to integrate data obtained in these two types of monitoring into meaningful assessments has been the subject of recent efforts by the International Council for Exploration of the Sea (ICES) Expert Groups. Work within these groups has concentrated on defining a core set of chemical and biological endpoints that can be used across maritime areas, defining confounding factors, supporting parameters and protocols for measurement. The framework comprised markers for concentrations of, exposure to and effects from, contaminants. Most importantly, assessment criteria for biological effect measurements have been set and the framework suggests how these measurements can be used in an integrated manner alongside contaminant measurements in biota, sediments and potentially water. Output from this process resulted in OSPAR Commission (www.ospar.org) guidelines that were adopted in 2012 on a trial basis for a period of 3 years. The developed assessment framework can furthermore provide a suitable approach for the assessment of Good Environmental Status (GES) for Descriptor 8 of the European Union (EU) Marine Strategy Framework Directive (MSFD)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This paper reports a full assessment of results from ICON, an international workshop on marine integrated contaminant monitoring, encompassing different matrices (sediment, fish, mussels, gastropods), areas (Iceland, North Sea, Baltic, Wadden Sea, Seine estuary and the western Mediterranean) and endpoints (chemical analyses, biological effects). ICON has demonstrated the use of a framework for integrated contaminant assessment on European coastal and offshore areas. The assessment showed that chemical contamination did not always correspond with biological effects, indicating that both are required. The framework can be used to develop assessments for EU directives. If a 95% target were to be used as a regional indicator of MSFD GES, Iceland and offshore North Sea would achieve the target using the ICON dataset, but inshore North Sea, Baltic and Spanish Mediterranean regions would fail., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Dab (Limanda limanda) and haddock (Melanogrammus aeglefinus) were collected from coastal and offshore locations in the Baltic (dab only), North Sea (haddock from one location only) and Iceland. Blood was analysed for DNA strand breaks using the comet assay and liver samples for DNA adduct concentrations. DNA strand breaks were at background levels in dab from the two Iceland locations and from the Dogger Bank. The highest levels were observed in dab from the Firth of Forth, Ekofisk and the German Bight. Hepatic DNA adducts in dab were highest at Ekofisk, in the Baltic and Dogger Bank, below detection limit in dab from Iceland and low in dab from the Firth of Forth and German Bight. There was large variation in DNA strand breaks between locations and individuals for haddock, particularly from Iceland. Adduct concentrations were elevated in haddock from both Iceland and the Firth of Forth. A general linear model (GLM) suggested that, in addition to location, the size of dab and its general condition contributed to explaining the observed variability in DNA strand breaks. A GLM for adducts in dab similarly allocated most of the variability to location, but with a possible contribution from CYP1A activity. There were no apparent differences between male and female dab for any of the methods. There was no obvious relationship between strand breaks and adducts in the same fish although dab from Ekofisk and Iceland had respectively high and low responses using both methods. The results from this large-scale study showed pollution-related genotoxicity for dab, that fish blood samples can be conserved prior to comet analyses and that there are clear species differences in genotoxic responses even when collected at the same location., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

An international workshop on marine integrated contaminant monitoring (ICON) was organised to test a framework on integrated environmental assessment and simultaneously assess the status of selected European marine areas. Biota and sediment were sampled in selected estuarine, inshore and offshore locations encompassing marine habitats from Iceland to the Spanish Mediterranean. The outcome of the ICON project is reported in this special issue as method-oriented papers addressing chemical analyses, PAH metabolites, oxidative stress, biotransformation, lysosomal membrane stability, genotoxicity, disease in fish, and sediment assessment, as well as papers assessing specific areas. This paper provides a background and introduction to the ICON project, by reviewing how effects of contaminants on marine organisms can be monitored and by describing strategies that have been employed to monitor and assess such effects. Through the ICON project we have demonstrated the use of an integrating framework and gleaned more knowledge than ever before in any single field campaign about the impacts contaminants may have in European marine areas., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In the framework of the ICON project (Integrated Assessment of Contaminant Impacts on the North Sea), muscle tissue from a total of 135 common dab (Limanda limanda) (20-28 cm total length) was collected in seven offshore sampling areas in the North Sea, at Iceland and in the Baltic Sea during Aug/Sept and December 2008 for a chemical mercury speciation analysis by means of gas chromatography and detection by cold vapour atomic fluorescence spectroscopy (GC-CVAFS). There was a highly significant correlation between concentrations of methylmercury (MeHg + ) and inorganic mercury (Hg 2+ ) in individual fish, and the mean ratio of MeHg + compared to Σ Hg (MeHg +  + Hg 2+ ) was 94.0%. The results revealed statistically significant differences in concentrations of MeHg + and Hg 2+ , respectively, between sampling areas. Mean concentrations in the German Bight (North Sea), in Icelandic waters and in Mecklenburg Bight (Baltic Sea) were low (MeHg + : 0.023-0.036; Hg 2+ : 0.001-0.002 mg/kg wet weight), while concentrations in dab from the Dogger Bank, Firth of Forth and the vicinity of the Ekofisk oil field (all North Sea) were significantly higher (MeHg + : 0.059-0.101; Hg 2+ : 0.003-0.004 mg/kg wet weight). Statistical correlation analysis on effects of host-specific factors revealed that neither length, weight, age, sex nor condition factor showed a significant relationship with Hg concentrations. However, Hg concentrations were significantly correlated with the Fish Disease Index (FDI), indicating a relationship between Hg concentrations and the health status of dab. Multiple linear regression analysis aiming to find factors affecting Hg concentrations revealed that only the sampling area had a highly significant main effect on Hg concentrations, and in some cases, additionally the condition factor contributed significantly to the final model. From the results, it cannot be excluded that elevated Hg concentration recorded in dab were linked to discharges from offshore oil and gas installations and that Hg affected the health status of dab., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Treatment delivery factors (i.e., therapist adherence, therapist competence, and therapeutic alliance) are considered to be important for cognitive behavioral therapy (CBT) for panic disorder and agoraphobia (PD/AG). In the current study, four independent raters conducted process evaluations based on 168 two-hour videotapes of 84 patients with PD/AG treated with exposure-based CBT. Two raters evaluated patients' interpersonal behavior in Session 1. Two raters evaluated treatment delivery factors in Session 6, in which therapists provided the rationale for conducting exposure exercises. At the 6-month follow-up, therapists' adherence (r=0.54) and therapeutic alliance (r=0.31) were significant predictors of changes in agoraphobic avoidance behavior; therapist competence was not associated with treatment outcomes. Patients' interpersonal behavior in Session 1 was a significant predictor of the therapeutic alliance in Session 6 (r=0.17). The findings demonstrate that treatment delivery factors, particularly therapist adherence, are relevant to the long-term success of CBT for PD/AG., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Plastic ingestion by marine biota has been reported for a variety of different taxa. In this study, we investigated 290 gastrointestinal tracts of demersal (cod, dab and flounder) and pelagic fish species (herring and mackerel) from the North and Baltic Sea for the occurrence of plastic ingestion. In 5.5% of all investigated fishes, plastic particles were detected, with 74% of all particles being in the microplastic (<5mm) size range. The polymer types of all found particles were analysed by means of Fourier transform infrared (FT-IR) spectroscopy. Almost 40% of the particles consisted of polyethylene (PE). In 3.4% of the demersal and 10.7% of the pelagic individuals, plastic ingestion was recorded, showing a significantly higher ingestion frequency in the pelagic feeders. The condition factor K was calculated to test differences in the fitness status between individuals with and without ingested plastic, but no direct effect was detected., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Study Objective: To identify the lengthiest step of total laparoscopic hysterectomy (TLH) in a teaching hospital and to determine which clinical factors affect the duration of this step., Setting: The University of Louisville Hospital., Design: Single institution retrospective case series., Methods and Main Results: This is a retrospective chart and video review that included 135 benign, elective TLHs performed at The University of Louisville. TLH was divided into 5 steps: (1) insertion of laparoscopic ports and adhesiolysis to restore normal anatomy; (2) identification of the ureter and resection of adnexal structures to transection of the round ligament; (3) transection of the round ligament to transection of the uterine artery; (4) lateralization of the uterine vessel pedicle to completion of colpotomy; and (5) completion of vaginal cuff closure. The random intercept and slope model was used to identify the lengthiest step of TLH, and the backward elimination procedure was used to evaluate which clinical factors affected this step. Mean ± SD total length of TLH was 81 ± 30 min. The lengthiest step was colpotomy, with a mean duration of 24 ± 13 min. Uterine weight significantly increased the length of time required for colpotomy (p = .001). The primary energy source (ultrasonic scalpel vs monopolar hook) used to perform colpotomy did not influence the length of time (p = .539 vs p = .583). Uterine weight (p < .001) and adhesiolysis (p = .003) significantly increased the total time of TLH., Conclusions: At a teaching institution where surgeries are performed by residents and fellows, colpotomy is the lengthiest step of TLH and is influenced by uterine weight. This finding may reflect the training levels of the surgeons performing these cases and the learning curve associated with a challenging surgical skill. Further research should focus on simulation models and/or tools for colpotomy that may result in greater efficiency in the operating room., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To review the indications, rationale, and technique for abdominal cerclage, specifically focusing on a laparoscopic approach to this procedure during the first trimester of pregnancy., Design: This is an educational video directed toward gynecologic surgeons. Patient consent was obtained for use of surgical video footage, and Institutional Review Board exemption was granted. A patient case is discussed and a step-by-step description of the technique used to perform laparoscopic cerclage in the first trimester of pregnancy is demonstrated using surgical footage., Setting: The estimated incidence of cervical insufficiency affecting pregnancy is as high as 1%. Cervical cerclage placement is the treatment for this condition. Although most cerclages are placed transvaginally via the Shirodkar or McDonald technique, abdominal cerclage is necessary in women with a previous failed transvaginal cerclage or in those with minimal cervical tissue accessible vaginally [1,2]. Both laparoscopic and robotic approaches to this procedure have been developed, allowing patients to enjoy a more rapid recovery as well as to avoid an unnecessary laparotomy[3-6]. The observational studies reporting outcomes for laparoscopic-assisted abdominal cerclage quote fetal survival rates of >85%, which is comparable to the rates for abdominal cerclage[7-18]. Complication rates are low, also congruent with the laparotomic approach[12-18]., Intervention: The patient, a 35-year-old gravida 3, para 1, 0, 1, 1, at 11 weeks gestation, had a history of a full-term vaginal delivery followed by an excisional procedure for cervical dysplasia, and then an early second trimester pregnancy loss. She was referred for laparoscopic-assisted abdominal cerclage after a severely shortened cervix was noted on examination. Laparoscopic cerclage placement was uncomplicated, with minimal blood loss encountered. The patient did well in the immediate postoperative period and was discharged home on postoperative day 1. The remainder of the pregnancy was uneventful, and she delivered via scheduled cesarean section at term., Conclusion: With proper patient selection and operative planning, the technique of laparoscopic cerclage is both safe and advantageous in terms of faster recovery. Obstetric outcomes are equivalent, if not superior, to an open abdominal approach to this procedure., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Polyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake., Objective: We aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk., Design: Osteoporotic fractures were determined from medical records over 5-9 y of follow-up in men and women aged 66-96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression., Results: In men, the highest tertile of PUFAs, n-3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98)., Conclusions: Greater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n-3 fatty acid consumption may differ by sex., (© 2015 American Society for Nutrition.)

The potentially detrimental effects of safety behaviors during exposure therapy are still subject to debate. Empirical findings are inconsistent, and few studies have investigated effects of idiosyncratic safety behavior manifestations during exposure or in everyday life. These limitations might be due to a lack of appropriate measures that address individual safety behaviors. We examined psychometric properties and predictive value of the Texas Safety Maneuver Scale (TSMS), a questionnaire specifically targeting safety behaviors in panic disorder and agoraphobia. Effects of safety behavior use, both during everyday life and during therapy, were examined using data from a multicenter RCT of N=268 patients that aimed at evaluating efficacy and mechanisms of action of two variants of an exposure-based therapy. The TSMS total score demonstrated good internal consistency (α=0.89), and it showed significant correlations with selected measures of baseline anxiety and impairment. The proposed factor structure could not be replicated. Frequent safety behavior use at baseline was associated with actual safety behavior during exposure exercises. Pronounced in-situ safety behavior, but not baseline safety behavior was associated to detrimental treatment outcome. The results underline the relevance of a rigorous safety behavior assessment in therapy. The actual relationship between safety behavior use and treatment outcome is yet to determine., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The purpose of the study was to contrast first panic attacks (PAs) of patients with panic disorder (PD) with vs. without agoraphobia and to explore differences between first PAs leading to the development of PD and those that remain isolated. Data were drawn from a community survey (N=2259 including 88 isolated PAs and 75 PD cases). An additional sample of 234 PD patients was recruited in a clinical setting. A standardized interview assessed the symptoms of the first PA, context of its occurrence and subsequent coping attempts. Persons who developed PD reported more severe first PAs, more medical service utilization and exposure-limiting coping attempts than those with isolated PAs. The context of the first PA did not differ between PD and isolated PAs. PD with agoraphobia was specifically associated with greater symptom severity and occurrence of first attacks in public. Future research should validate these findings using a longitudinal approach., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The data on environmental genotoxicity and cytotoxicity levels as well as on genotoxicity risk in flounder (Platichthys flesus), herring (Clupea harengus) and cod (Gadus morhua) collected in 2010-2012 at 42 stations located in chemical munitions dumping areas of the southern Baltic Sea are presented. The frequency of micronuclei, nuclear buds and nucleoplasmic bridges in erythrocytes was used as genotoxicity endpoint and the induction of fragmented-apoptotic, bi-nucleated and 8-shaped erythrocytes as cytotoxicity endpoint. The most significantly increased geno-cytotoxicity levels were determined in fish collected near known chemical munitions dumpsites. Extremely high genotoxicity risk for flounder were identified at 21 out of 24 stations, for herring at 29 out of 31 and for cod at 5 out of 10 stations studied. The reference level of genotoxicity was not recorded at any of the stations revealing that in the sampling area fish were affected generally., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In the framework of the ICON project, environmental genotoxicity and cytotoxicity levels were assessed in blood erythrocytes of dab (Limanda limanda) and haddock (Melanogrammus aeglefinus) collected at 25 stations in the North Sea and near the coast of Iceland in August-October 2008. Micronuclei, nuclear buds and bi-nucleated cells with nucleoplasmic bridges were assessed as environmental genotoxicity biomarkers, and the frequency of fragmented-apoptotic and bi-nucleated erythrocytes were assessed as environmental cytotoxicity biomarkers. The lowest frequencies of genotoxic and cytotoxic abnormalities were detected in fish from the Icelandic study stations. The highest frequencies of abnormalities were recorded in dab from the Dogger Bank and the German Bight, in haddock from the Egersund Bank and from an area off the Firth of Forth (North Sea). In fish from the Icelandic reference area, frequencies of genotoxicity and cytotoxicity responses were significantly lower than in fish from most areas of the North Sea., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The use of liver histopathology in various fish species as a biomarker in marine monitoring programmes to assess the biological effect of exposure to anthropogenic contaminants is well established. However, although the eelpout (Zoarces viviparus) has repeatedly been recommended as an appropriate bioindicator for monitoring purposes in the Baltic Sea, information on histopathological liver alterations of this species is scarce. In order to obtain an overview, a total of 1070 eelpout, collected in the period between spring 2001 and winter 2010 from 34 sampling sites distributed over large parts of the Baltic Sea, were histologically analyzed. Liver lesions were recorded and classified according to established liver lesion categories. A high prevalence of non-specific and early toxicopathic non-neoplastic hepatic lesions was recorded. In contrast, pre-neoplastic lesions were observed only in rare cases and neoplastic changes were absent. A comparison with published data on other fish species revealed that the observed alterations may indicate effects of environmental stressors including contaminants. The results of the present study, thus, support the application of eelpout liver histopathology in environmental monitoring., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG)., Methods: Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test., Results: Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks., Conclusions: We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

In scientific publications, laboratory and clinical images are part of the evidence on which authors base the interpretation and conclusions of their research. However, variability in biology, image acquisition and quality, standards for interpretation, training and experience of evaluators, and presence of artifacts can markedly reduce interrater and intrarater reliability. This variability in interpretation suggests that authors should support their claims with complete information about the image on which those claims are based. Yet, without appropriate guidelines, the documentation of these published images almost certainly will be incomplete and inconsistent. Here, we propose six principles for documenting clinical and laboratory images in publications: the clinical and laboratory images in publications (CLIP) principles. The principles were inspired by the CONSORT (Consolidated Standards of Reporting Trials) and related initiatives that are intended to improve the documentation of research through the use of guidelines. However, the CLIP principles are not formal guidelines, standards, or requirements but, rather, reminders about the information that may be needed to support interpretations and conclusions based on images. These principles organize the self-evident factors related to the nature, acquisition, reporting, and presentation of clinical and laboratory images. As imaging technologies become more complex, however, so too does the specific information needed to document how specific types of images are acquired. Thus, in addition to general direction for all authors, the CLIP principles give journals and professional societies a foundation, a direction, and some models to assist them in developing technology-specific guidelines for reporting the images common in their area of practice.

Environmental genotoxicity was investigated at 82 locations encompassing different regions of the Baltic Sea. Micronuclei (MN) analysis was performed in erythrocytes of 1892 specimens of flounder Platichthys flesus, herring Clupea harengus and eelpout Zoarces viviparus, three of the most common native fish species of the Baltic Sea collected in 2009-2011. MN background levels in fish were determined using data obtained in 2001-2011 from 107 Baltic sites. Extremely high genotoxicity risk zones were found for flounder at 11 stations out of 16 in 2009 and 33 stations of 41 in 2010-2011, for herring, at 5 of 18 stations in 2009 and 20 of 43 stations in 2010-2011, in eelpout only at one out of 29 stations. The sampling stations were restricted mainly to the southern and eastern Baltic Sea offshore zones and in most of them, MN frequencies in flounder and herring significantly exceeded the reference and background levels of micronuclei. This is a first attempt to evaluate the background MN responses, as well as low, high and extremely high genotoxicity risk levels for native fish species., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Flounder (Platichthys flesus), collected in late fall of 2009 from four coastal sites in the southern Baltic Sea including the Gulf of Gdańsk (GoG), were investigated for a suite of biomarkers of contaminant effects. The biomarkers included liver histopathologies, which were diagnosed and assessed using commonly applied lesion categories, the size and density of melano-macrophage aggregates (MMAs), expression of proliferating cell nuclear antigen (PCNA) and of cytochrome P450 1A (CYP1A) in liver as well as the size and density of MMAs and density of Perls'-positive cells in the spleen. The prevalence of liver lesions differed among the sites. Most frequently occurring were non-specific and early toxicopathic non-neoplastic lesions. Mean MMA size was in the range of 264-519 μm(2) and 717-2137 μm(2) in liver and spleen, respectively, and density was in the range of 6-13 and 15-26 MMAmm(-2), respectively. Mean density of PCNA-positive hepatocytes was in the range of 300-1281 cellsmm(-2). These histomorphometrical biomarkers correlated positively with the muscle Hg, Σ(7)PCB, and ΣDDT residues and negatively with the indices of general liver condition. They showed significant differences between the sites, which were in line with the spatial prevalence of liver lesions and CYP1A induction. Overall, the biomarker responses were more pronounced in the GoG sites in comparison to those outside the Gulf, which confirms some earlier results and broadens the knowledge of contaminant effects in the Polish coastal zone of the Baltic Sea., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although functional magnetic resonance imaging (fMRI) has gained increasing importance in investigating neural substrates of anxiety disorders, less is known about the stress eliciting properties of the scanner environment itself. The aim of the study was to investigate feasibility, self-reported distress and anxiety management strategies during an fMRI experiment in a comprehensive sample of patients with panic disorder and agoraphobia (PD/AG). Within the national research network PANIC-NET, n=89 patients and n=90 controls participated in a multicenter fMRI study. Subjects completed a retrospective questionnaire on self-reported distress, including a habituation profile and exploratory questions about helpful strategies. Drop-out rates and fMRI quality parameters were employed as markers of study feasibility. Different anxiety measures were used to identify patients particularly vulnerable to increased scanner anxiety and impaired data quality. Three (3.5%) patients terminated the session prematurely. While drop-out rates were comparable for patients and controls, data quality was moderately impaired in patients. Distress was significantly elevated in patients compared to controls; claustrophobic anxiety was furthermore associated with pronounced distress and lower fMRI data quality in patients. Patients reported helpful strategies, including motivational factors and cognitive coping strategies. The feasibility of large-scale fMRI studies on PD/AG patients could be proved. Study designs should nevertheless acknowledge that the MRI setting may enhance stress reactions. Future studies are needed to investigate the relationship between self-reported distress and fMRI data in patient groups that are subject to neuroimaging research., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background & Aims: Pegylated interferon (PEG-IFN) alfa-2b plus ribavirin (RBV) is the standard of care for adults with chronic hepatitis C but was not approved for the treatment of children at the time of this study. The aim of this study was to evaluate the efficacy and safety of PEG-IFN alfa-2b plus RBV in children., Methods: Children and adolescents ages 3-17 years were treated with PEG-IFN alfa-2b (60microg/m(2)/week) plus RBV (15mg/kg/day). The duration of therapy was 24 weeks for genotype (G) 2 and G3 patients with low viral load (<600,000IU/ml) and 48 weeks for G1, G4, and G3 with high viral load (>or=600,000IU/ml). The primary end point was sustained virologic response (SVR), defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of therapy., Results: SVR was attained by 70 (65%) children. Genotype was the main predictor of response: G1, 53%; G2/3, 93%; G4, 80%. SVRs were similar in younger and older children. Baseline viral load was the main predictor of response in the G1 cohort. No new safety signals were identified, and adverse events (AEs) were generally mild or moderate in severity. Dose was modified because of AEs in 25% of children; 1 child discontinued because of an AE (thrombocytopenia). No serious AEs related to study drugs were reported., Conclusion: Therapy with PEG-IFN alfa-2b plus RBV in children and adolescents with chronic hepatitis C offers favorable efficacy, reduced injection frequency, and an acceptable safety profile.

Micronuclei (MN), nuclear buds (NB) and fragmented-apoptotic cells (FA) were analyzed in mature peripheral blood and immature cephalic kidney erythrocytes of flounder (Platichthys flesus), dab (Limanda limanda) and cod (Gadus morhua) from 12 offshore sites in the Baltic Sea (479 specimens) and 11 sites in the North Sea (291 specimens), which were collected during three research vessel cruises in December 2002, 2003 and in September 2004. The highest levels of environmental genotoxicity (frequencies of MN up to 0.5 per thousand, NB - up to 0.75 per thousand) and cytotoxicity (FA - up to 0.53 per thousand) were observed in flatfishes from areas close to oil and gas platforms in the North Sea and in zones related to the extensive shipping and potentially influenced by contamination from large European Rivers (Elbe, Vistula, Oder). In dab from the offshore zones of the North Sea, the levels of nuclear abnormalities were higher as compared to those in dab from the Baltic Sea. Responses in immature kidney erythrocytes were higher than in mature erythrocytes from peripheral blood. MN frequency lower than 0.05 per thousand (the Baltic Sea) and lower than 0.1 per thousand (the North Sea) could be suspected as a reference level in the peripheral blood erythrocytes of flatfish.

Objectives: Clinical research related to the management of the syndrome of temporomandibular joint pain and dysfunction would be facilitated enormously between researchers in different locations around the world if a small number of patient-oriented questionnaires were to achieve wide acceptance. It would make comparison of therapeutic results possible. For this reason, a cross-cultural version of the Jaw Pain and Function (JPF)-Questionnaire was developed and validated for use in German-speaking patients with functional temporomandibular disorders., Material and Methods: The scale was translated from the English into the German language and translated back into English again, pretested and reviewed by a committee. The German version of the JPF-Questionnaire was tested on 137 patients with temporomandibular disorders. Reliability and concurrent construct validity were assessed using Pearson's correlation coefficients., Results: The concurrent validity was assessed by evaluating the relation of the questionnaire's summary score (the internal criterion) to data on maximum interincisal distance (the external criterion). Spearman's and correlation coefficients were statistically significant for the comparison of the summary score with maximal mouth opening (r=-0.213; p=0.036). Test-retest reliability for the JPF-Questionnaire was also assessed by Spearman's correlation coefficients: at first admission at the clinic (time a, mean=20.23+/-16.42, median=16), then at the time of administration 1 day later at home (time b, mean=17.98+/-16.29, median=13), and 7 days later at home (time c, mean=17.90+/-15.77, median=13). They were r=0.91 (p=0.0001) for the initial administration with the repetition 1 day later, r=0.90 (p=0.0001) for the initial administration with the repetition 1 week later, and r=0.93 (p=0.0001) for the correlation between the two repetitions. Test - retest reliability measured by mean-against-difference graphs was not satisfactory for time (a) versus time (b) and time (a) versus time (c) but there was a good test-retest reliability for time (b) versus time (c)., Conclusion: The use of this instrument can be recommended in future clinical trials, as the German version of the JPF-Questionnaire seems to be valid and--under the same test-retest conditions--reliable for the assessment of temporomandibular joint disorders.