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BACKGROUND: Canine parvovirus (CPV) is a common cause of enteritis, immune suppression and systemic inflammation in young dogs. Endothelial markers, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and molecules that upregulate their expression, such as high mobility group box 1 protein (HMGB-1), provide insight into the state of the endothelium during inflammation. OBJECTIVES: This study aimed to determine if circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 were altered in CPV enteritis compared to healthy controls, and whether a correlation existed between these molecules and the degree of inflammation METHODS: Thirty dogs with naturally occurring CPV enteritis and ten control dogs were included. Physical examinations, complete blood count and C-reactive protein (CRP) measurements were performed on all dogs at presentation. The concentrations of ICAM-1, VCAM-1 and HMGB-1 were measured using commercially available canine-specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: In dogs with CPV enteritis, ICAM-1 concentrations were significantly lower (median: 5.9 [IQR: 4.3-8.3]) and CRP higher (134 [IQR: 85-195]) compared to controls (8.0 [IQR: 6.9-10.3], p = 0.008; 1 [IQR: 0-7], p < 0.001). No significant difference was found for VCAM-1 and HMGB-1. A strong correlation was identified between VCAM-1 and segmented neutrophil count (r = 0.612, p < 0.001). CONCLUSION: Despite the presence of systemic inflammation in CPV enteritis, evidenced by high CRP concentrations, our results suggest circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 failed to show an increase. Endothelial activation with subsequent leukocyte adhesion and transmigration through the endothelium may be affected in CPV enteritis and these findings require further investigation.

Contains fulltext : 287661.pdf (Publisher’s version ) (Closed access) BACKGROUND: Vilobelimab, an anti-C5a monoclonal antibody, was shown to be safe in a phase 2 trial of invasively mechanically ventilated patients with COVID-19. Here, we aimed to determine whether vilobelimab in addition to standard of care improves survival outcomes in this patient population. METHODS: This randomised, double-blind, placebo-controlled, multicentre phase 3 trial was performed at 46 hospitals in the Netherlands, Germany, France, Belgium, Russia, Brazil, Peru, Mexico, and South Africa. Participants aged 18 years or older who were receiving invasive mechanical ventilation, but not more than 48 h after intubation at time of first infusion, had a PaO(2)/FiO(2) ratio of 60-200 mm Hg, and a confirmed SARS-CoV-2 infection with any variant in the past 14 days were eligible for this study. Eligible patients were randomly assigned (1:1) to receive standard of care and vilobelimab at a dose of 800 mg intravenously for a maximum of six doses (days 1, 2, 4, 8, 15, and 22) or standard of care and a matching placebo using permuted block randomisation. Treatment was not continued after hospital discharge. Participants, caregivers, and assessors were masked to group assignment. The primary outcome was defined as all-cause mortality at 28 days in the full analysis set (defined as all randomly assigned participants regardless of whether a patient started treatment, excluding patients randomly assigned in error) and measured using Kaplan-Meier analysis. Safety analyses included all patients who had received at least one infusion of either vilobelimab or placebo. This study is registered with ClinicalTrials.gov, NCT04333420. FINDINGS: From Oct 1, 2020, to Oct 4, 2021, we included 368 patients in the ITT analysis (full analysis set; 177 in the vilobelimab group and 191 in the placebo group). One patient in the vilobelimab group was excluded from the primary analysis due to random assignment in error without treatment. At least one dose of study treatment was given to 364 (99%) patients (safety analysis set). 54 patients (31%) of 177 in the vilobelimab group and 77 patients (40%) of 191 in the placebo group died in the first 28 days. The all-cause mortality rate at 28 days was 32% (95% CI 25-39) in the vilobelimab group and 42% (35-49) in the placebo group (hazard ratio 0·73, 95% CI 0·50-1·06; p=0·094). In the predefined analysis without site-stratification, vilobelimab significantly reduced all-cause mortality at 28 days (HR 0·67, 95% CI 0·48-0·96; p=0·027). The most common TEAEs were acute kidney injury (35 [20%] of 175 in the vilobelimab group vs 40 [21%] of 189 in the placebo), pneumonia (38 [22%] vs 26 [14%]), and septic shock (24 [14%] vs 31 [16%]). Serious treatment-emergent adverse events were reported in 103 (59%) of 175 patients in the vilobelimab group versus 120 (63%) of 189 in the placebo group. INTERPRETATION: In addition to standard of care, vilobelimab improves survival of invasive mechanically ventilated patients with COVID-19 and leads to a significant decrease in mortality. Vilobelimab could be considered as an additional therapy for patients in this setting and further research is needed on the role of vilobelimab and C5a in other acute respiratory distress syndrome-causing viral infections. FUNDING: InflaRx and the German Federal Government.

Background. Nursing students face dual stress from a combination of academic and clinical demands, which may affect their emotional wellbeing. Poor emotional wellbeing may prevent them from gaining the necessary knowledge and skills to care for patients. Objectives. To describe and compare levels of emotional exhaustion, personal accomplishment, compassion satisfaction, compassion fatigue and perceived stress of undergraduate and postgraduate nursing students, and to determine the influence of compassion fatigue, perceived stress and disengaged coping on emotional exhaustion. Methods. This study was a cross-sectional descriptive survey at a purposively selected South African university. There were 685 students, of whom 471 (68.8%) completed the questionnaire, which comprised a biographical section, as well as standardised and validated scales. Results. The respondents obtained a moderate score for perceived stress and were at average risk for emotional exhaustion and compassion fatigue. There were statistically significant differences between undergraduates and postgraduates on all scales, with undergraduates faring the worst. Stress from assignments and workload, lack of professional knowledge and skills, teachers and nursing staff and compassion fatigue made a statistically significant contribution to the prediction of emotional exhaustion in undergraduates. Compassion fatigue and stress from assignments and workload made a statistically significant contribution to the prediction of emotional exhaustion in postgraduates. Conclusion. Nursing students had moderate stress scores and were at average risk for emotional exhaustion and compassion fatigue, with undergraduate students faring the worst. Schools of nursing should prioritise the emotional wellbeing of their students, particularly that of undergraduates.

Blood pressure measurement is a marker of antenatal care quality. In well resourced settings, lower blood pressure cutoffs for hypertension are associated with adverse pregnancy outcomes. We aimed to study the associations between blood pressure thresholds and adverse outcomes and the diagnostic test properties of these blood pressure cutoffs in low-resource settings.We did a secondary analysis of data from 22 intervention clusters in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials (NCT01911494) in India (n=6), Mozambique (n=6), and Pakistan (n=10). We included pregnant women aged 15-49 years (12-49 years in Mozambique), identified in their community by trained community health workers, who had data on blood pressure measurements and outcomes. The trial was unmasked. Maximum blood pressure was categorised as: normal blood pressure (systolic blood pressure [sBP]120 mm Hg and diastolic blood pressure [dBP]80 mm Hg), elevated blood pressure (sBP 120-129 mm Hg and dBP80 mm Hg), stage 1 hypertension (sBP 130-139 mm Hg or dBP 80-89 mm Hg, or both), non-severe stage 2 hypertension (sBP 140-159 mm Hg or dBP 90-109 mm Hg, or both), or severe stage 2 hypertension (sBP ≥160 mm Hg or dBP ≥110 mm Hg, or both). We classified women according to the maximum blood pressure category reached across all visits for the primary analyses. The primary outcome was a maternal, fetal, or neonatal mortality or morbidity composite. We estimated dose-response relationships between blood pressure category and adverse outcomes, as well as diagnostic test properties.Between Nov 1, 2014, and Feb 28, 2017, 21 069 women (6067 in India, 4163 in Mozambique, and 10 839 in Pakistan) contributed 103 679 blood pressure measurements across the three CLIP trials. Only women with non-severe or severe stage 2 hypertension, as discrete diagnostic categories, experienced more adverse outcomes than women with normal blood pressure (risk ratios 1·29-5·88). Using blood pressure categories as diagnostic thresholds (women with blood pressure within the category or any higher category vs those with blood pressure in any lower category), dose-response relationships were observed between increasing thresholds and adverse outcomes, but likelihood ratios were informative only for severe stage 2 hypertension and maternal CNS events (likelihood ratio 6·36 [95% CI 3·65-11·07]) and perinatal death (5·07 [3·64-7·07]), particularly stillbirth (8·53 [5·63-12·92]).In low-resource settings, neither elevated blood pressure nor stage 1 hypertension were associated with maternal, fetal, or neonatal mortality or morbidity adverse composite outcomes. Only the threshold for severe stage 2 hypertension met diagnostic test performance standards. Current diagnostic thresholds for hypertension in pregnancy should be retained.University of British Columbia, the BillMelinda Gates Foundation.

Canine parvovirus (CPV) is a common cause of enteritis, immune suppression and systemic inflammation in young dogs. Endothelial markers, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and molecules that upregulate their expression, such as high mobility group box 1 protein (HMGB-1), provide insight into the state of the endothelium during inflammation. This study aimed to determine if circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 were altered in CPV enteritis compared to healthy controls, and whether a correlation existed between these molecules and the degree of inflammation. Thirty dogs with naturally occurring CPV enteritis and ten control dogs were included. Physical examinations, complete blood count and C-reactive protein (CRP) measurements were performed on all dogs at presentation. The concentrations of ICAM-1, VCAM-1 and HMGB-1 were measured using commercially available canine-specific enzyme-linked immunosorbent assay (ELISA) kits. In dogs with CPV enteritis, ICAM-1 concentrations were significantly lower (median: 5.9 [IQR: 4.3-8.3]) and CRP higher (134 [IQR: 85-195]) compared to controls (8.0 [IQR: 6.9-10.3]

Top predators are important components of healthy ecosystems but are at risk of overexploitation due to insufficient data on life-history characteristics and population dynamics to guide management...

Summary Background To overcome the three delays in triage, transport and treatment that underlie adverse pregnancy outcomes, we aimed to reduce all-cause adverse outcomes with community-level interventions targeting women with pregnancy hypertension in three low-income countries. Methods In this individual participant-level meta-analysis, we de-identified and pooled data from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials in Mozambique, Pakistan, and India, which were run in 2014–17. Consenting pregnant women, aged 12–49 years, were recruited in their homes. Clusters, defined by local administrative units, were randomly assigned (1:1) to intervention or control groups. The control groups continued local standard of care. The intervention comprised community engagement and existing community health worker-led mobile health-supported early detection, initial treatment, and hospital referral of women with hypertension. For this meta-analysis, as for the original studies, the primary outcome was a composite of maternal or perinatal outcome (either maternal, fetal, or neonatal death, or severe morbidity for the mother or baby), assessed by unmasked trial surveillance personnel. For this analysis, we included all consenting participants who were followed up with completed pregnancies at trial end. We analysed the outcome data with multilevel modelling and present data with the summary statistic of adjusted odds ratios (ORs) with 95% CIs (fixed effects for maternal age, parity, maternal education, and random effects for country and cluster). This meta-analysis is registered with PROSPERO, CRD42018102564. Findings Overall, 44 clusters (69 330 pregnant women) were randomly assigned to intervention (22 clusters [36 008 pregnancies]) or control (22 clusters [33 322 pregnancies]) groups. 32 290 (89·7%) pregnancies in the intervention group and 29 698 (89·1%) in the control group were followed up successfully. Median maternal age of included women was 26 years (IQR 22–30). In the intervention clusters, 6990 group and 16 691 home-based community engagement sessions and 138 347 community health worker-led visits to 20 819 (57·8%) of 36 008 women (of whom 11 095 [53·3%] had a visit every 4 weeks) occurred. Blood pressure and dipstick proteinuria were assessed per protocol. Few women were eligible for methyldopa for severe hypertension (181 [1%] of 20 819) or intramuscular magnesium sulfate for pre-eclampsia (198 [1%]), of whom most accepted treatment (162 [89·5%] of 181 for severe hypertension and 133 [67·2%] of 198 for pre-eclampsia). 1255 (6%) were referred to a comprehensive emergency obstetric care facility, of whom 864 (82%) accepted the referral. The primary outcome was similar in the intervention (7871 [24%] of 32 290 pregnancies) and control clusters (6516 [22%] of 29 698; adjusted OR 1·17, 95% CI 0·90–1·51; p=0·24). No intervention-related serious adverse events occurred, and few adverse effects occurred after in-community treatment with methyldopa (one [2%] of 51; India only) and none occurred after in-community treatment with magnesium sulfate or during transport to facility. Interpretation The CLIP intervention did not reduce adverse pregnancy outcomes. Future community-level interventions should expand the community health worker workforce, assess general (rather than condition-specific) messaging, and include health system strengthening. Funding University of British Columbia, a grantee of the Bill & Melinda Gates Foundation.

Supplemental Digital Content is available in the text., In pregnancy in well-resourced settings, limited data suggest that higher blood pressure (BP) visit-to-visit variability may be associated with adverse pregnancy outcomes. Included were pregnant women in 22 intervention clusters of the CLIP (Community-Level Interventions for Preeclampsia) cluster randomized trials, who had received at least 2 prenatal contacts from a community health worker, including standardized BP measurement. Mixed-effects adjusted logistic regression assessed relationships between pregnancy outcomes and both BP level (median [interquartile range]) and visit-to-visit variability (SD and average real variability [ARV], adjusted for BP level), among all women and those who became hypertensive. The primary outcome was the CLIP composite of maternal and perinatal mortality and morbidity. Among 17 770 pregnancies, higher systolic and diastolic BP levels were associated with increased odds of the composite outcome per 5 mm Hg increase in BP (odds ratio [OR], 1.05 [95% CI, 1.03–1.07] and OR, 1.08 [1.06–1.11], respectively). Higher BP visit-to-visit variability was associated with increased odds, per a SD increase in BP variability measure, of (1) hypertension (systolic: OR, 2.09 [1.98–2.21] for SD and 1.52 [1.45–1.60] for ARV; diastolic: OR, 2.70 [2.54–2.87] for SD and 1.86 [1.76–1.96] for ARV); and (2) the composite outcome (systolic: OR, 1.10 [1.06–1.14] for SD and 1.06 [1.02–1.10] for ARV; diastolic: OR, 1.07 [1.03–1.11] for SD and 1.06 [1.02–1.09] for ARV). In 3 less-developed countries, higher BP level and visit-to-visit variability predicted adverse pregnancy outcomes, providing an opportunity for high-definition medicine.

Background The African continent is comprised of several different biomes, although savanna is the most prevalent. The current heterogeneous landscape was formed through long-term vegetation shifts as a result of the global cooling trend since the Oligocene epoch. The overwhelming trend was a shift from primarily forest, to primarily savanna. As such, faunal groups that emerged during the Paleogene/Neogene period and have species distributed in both forest and savanna habitat should show a genetic signature of the possible evolutionary impact of these biome developments. Crotaphopeltis and Philothamnus (Colubridae) are excellent taxa to investigate the evolutionary impact of these biome developments on widespread African colubrid snakes, and whether timing and patterns of radiation are synchronous with biome reorganisation. Methods A phylogenetic framework was used to investigate timing of lineage diversification. Phylogenetic analysis included both genera as well as other Colubridae to construct a temporal framework in order to estimate radiation times for Crotaphopeltis and Philothamnus. Lineage diversification was estimated in Bayesian Evolutionary Analysis Sampling Trees (BEAST), using two mitochondrial markers (cyt–b, ND4), one nuclear marker (c–mos), and incorporating one fossil and two biogeographical calibration points. Vegetation layers were used to classify and confirm species association with broad biome types (‘closed’ = forest, ‘open’ = savanna/other), and the ancestral habitat state for each genus was estimated. Results Philothamnus showed an ancestral state of closed habitat, but the ancestral habitat type for Crotaphopeltis was equivocal. Both genera showed similar timing of lineage diversification diverging from their sister genera during the Oligocene/Miocene transition (ca. 25 Mya), with subsequent species radiation in the Mid-Miocene. Philothamnus appeared to have undergone allopatric speciation during Mid-Miocene forest fragmentation. Habitat generalist and open habitat specialist species emerged as savanna became more prevalent, while at least two forest associated lineages within Crotaphopeltis moved into Afromontane forest habitat secondarily and independently. Discussion With similar diversification times, but contrasting ancestral habitat reconstructions, we show that these genera have responded very differently to the same broad biome shifts. Differences in biogeographical patterns for the two African colubrid genera is likely an effect of distinct life-history traits, such as the arboreous habits of Philothamnus compared to the terrestrial lifestyle of Crotaphopeltis.

Background Incomplete vital registration systems mean that causes of death during pregnancy and childbirth are poorly understood in low-income and middle-income countries. To inform global efforts to reduce maternal mortality, we compared physician review and computerised analysis of verbal autopsies (interpreting verbal autopsies [InterVA] software), to understand their agreement on maternal cause of death and circumstances of mortality categories (COMCATs) in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials. Methods The CLIP trials took place in India, Pakistan, and Mozambique, enrolling pregnant women aged 12-49 years between Nov 1, 2014, and Feb 28, 2017. 69 330 pregnant women were enrolled in 44 clusters (36 008 in the 22 intervention clusters and 33 322 in the 22 control clusters). In this secondary analysis of maternal deaths in CLIP, we included women who died in any of the 22 intervention clusters or 22 control clusters. Trained staff administered the WHO 2012 verbal autopsy after maternal deaths. Two physicians (and a third for consensus, if needed) reviewed trial surveillance data and verbal autopsies, and, in intervention clusters, community health worker-led visit data. They determined cause of death according to the WHO International Classification of Diseases-Maternal Mortality (ICD-MM). Verbal autopsies were also analysed by InterVA computer models (versions 4 and 5) to generate cause of death. COMCAT analysis was provided by InterVA-5 and, in India, by physician review of Maternal Newborn Health Registry data. Causes of death and COMCATs assigned by physician review, Inter-VA-4, and InterVA-5 were compared, with agreement assessed with Cohen's κ coefficient. Findings Of 61 988 pregnancies with successful follow-up in the CLIP trials, 143 maternal deaths were reported (16 deaths in India, 105 in Pakistan, and 22 in Mozambique). The maternal death rate was 231 (95% CI 193-268) per 100 000 identified pregnancies. Most deaths were attributed to direct maternal causes (rather than indirect or undetermined causes as per ICD-MM classification), with fair to good agreement between physician review and InterVA-4 (κ=0·56 [95% CI 0·43-0·66]) or InterVA-5 (κ=0·44 [0·30-0·57]), and InterVA-4 and InterVA-5 (κ=0·72 [0·60-0·84]). The top three causes of death were the same by physician review, InterVA-4, and InterVA-5 (ICD-MM categories obstetric haemorrhage, non-obstetric complications, and hypertensive disorders); however, attribution of individual patient deaths to obstetric haemorrhage varied more between methods (physician review, 38 [27%] deaths; InterVA-4, 69 [48%] deaths; and InterVA-5, 82 [57%] deaths), than did attribution to non-obstetric causes (physician review, 39 [27%] deaths; InterVA-4, 37 [26%] deaths; and InterVA-5, 28 [20%] deaths) or hypertensive disorders (physician review, 23 [16%] deaths; InterVA-4, 25 [17%] deaths; and InterVA-5, 24 [17%] deaths). Agreement for all nine ICD-MM categories was fair for physician review versus InterVA-4 (κ=0·48 [0·38-0·58]), poor for physician review versus InterVA-5 (κ=0·36 [0·27-0·46]), and good for InterVA-4 versus InterVA-5 (κ=0·69 [0·59-0·79]). The most commonly assigned COMCATs by InterVA-5 were emergencies (68 [48%] of 143 deaths) and health systems (62 [43%] deaths), and by physician review (India only) were health systems (seven [44%] of 16 deaths) and inevitability (five [31%] deaths); agreement between InterVA-5 and physician review (India data only) was poor (κ=0·04 [0·00-0·15]). Interpretation Our findings indicate that InterVA-5 is less accurate than InterVA-4 at ascertaining causes and circumstances of maternal death, when compared with physician review. Our results suggest a need to improve the next iteration of InterVA, and for researchers and clinicians to preferentially use InterVA-4 when recording maternal deaths. Funding University of British Columbia (grantee of the Bill & Melinda Gates Foundation).

Background The African continent is comprised of several different biomes, although savanna is the most prevalent. The current heterogeneous landscape was formed through long-term vegetation shifts as a result of the global cooling trend since the Oligocene epoch. The overwhelming trend was a shift from primarily forest, to primarily savanna. As such, faunal groups that emerged during the Paleogene/Neogene period and have species distributed in both forest and savanna habitat should show a genetic signature of the possible evolutionary impact of these biome developments. Crotaphopeltis and Philothamnus (Colubridae) are excellent taxa to investigate the evolutionary impact of these biome developments on widespread African colubrid snakes, and whether timing and patterns of radiation are synchronous with biome reorganisation. Methods A phylogenetic framework was used to investigate timing of lineage diversification. Phylogenetic analysis included both genera as well as other Colubridae to construct a temporal framework in order to estimate radiation times for Crotaphopeltis and Philothamnus. Lineage diversification was estimated in Bayesian Evolutionary Analysis Sampling Trees (BEAST), using two mitochondrial markers (cyt–b, ND4), one nuclear marker (c–mos), and incorporating one fossil and two biogeographical calibration points. Vegetation layers were used to classify and confirm species association with broad biome types (‘closed’ = forest, ‘open’ = savanna/other), and the ancestral habitat state for each genus was estimated. Results Philothamnus showed an ancestral state of closed habitat, but the ancestral habitat type for Crotaphopeltis was equivocal. Both genera showed similar timing of lineage diversification diverging from their sister genera during the Oligocene/Miocene transition (ca. 25 Mya), with subsequent species radiation in the Mid-Miocene. Philothamnus appeared to have undergone allopatric speciation during Mid-Miocene forest fragmentation. Habitat generalist and open habitat specialist species emerged as savanna became more prevalent, while at least two forest associated lineages within Crotaphopeltis moved into Afromontane forest habitat secondarily and independently. Discussion With similar diversification times, but contrasting ancestral habitat reconstructions, we show that these genera have responded very differently to the same broad biome shifts. Differences in biogeographical patterns for the two African colubrid genera is likely an effect of distinct life-history traits, such as the arboreous habits of Philothamnus compared to the terrestrial lifestyle of Crotaphopeltis.

This Commentary is a response to a Commentary published in the May/June 2020 issue: Nattrass N. Why are black South African students less likely to consider studying biological sciences? S Afr J Sci. 2020;116(5/6), Art. #7864, 2 pages. https://doi.org/10.17159/sajs.2020/7864 Responses to the Commentary in the May/June 2020 issue have been published collectively in a special issue of Volume 116.

ZusammenfassungDiese DVO Leitlinien, die in erster Linie für Allgemeinmediziner und Spezialisten für Knochenerkrankungen bestimmt sind, sollten von allen im klinischen und ambulanten Bereich tätigen medizinischen Fachkräften angewendet werden. Ziel der Leitlinie ist die Verbesserung der Diagnose, Prävention und Behandlung von Osteoporose und der Folgen der Erkrankung auf der Grundlage evidenzbasierter Medizin.Klare Empfehlungen, welche Patienten zu diagnostizieren und behandeln sind (basierend auf Risikofaktoren [einschließlich sekundärer Osteoporose]) sowie Primär-, Sekundär- oder Tertiärprävention werden dargestellt, mit dem Schwerpunkt auf der postmenopausalen Osteoporose und der Osteoporose bei Männern.Die Identifizierung von Patienten mit einem hohen Risiko für Frakturen wird hervorgehoben, und spezifische Schwellenwerte für die Intervention sind definiert (20 % Hüftfrakturrisiko innerhalb von 10 Jahren diagnostischer Schwellenwert, 30 % Hüftfrakturrisiko innerhalb von 10 Jahren therapeutische Schwelle). Die Diagnose von Osteoporose basiert auf der Anamnese des Patienten, der körperlichen Untersuchung, dem Funktionstest (z. B. Timed Up and Go Test), konventionellen Röntgenaufnahmen der Brust- und Lendenwirbelsäule und der Bestimmung der Knochenmineraldichte (BMD) durch das DXA Verfahren.Die Anamnese ist entscheidend für die Abschätzung des Frakturrisikos auf der Grundlage von 40 wissenschaftlich überprüften Risikofaktoren, die das Frakturrisiko mindestens verdoppeln (z. B. Begleiterkrankungen, Hüftfrakturen in der Familie, prävalente Frakturen an jedem Ort, Lebensstil, Anwendung von Medikamenten, körperliche Aktivität und Stürze). Röntgenaufnahmen der Brust- und Lendenwirbelsäule sind wichtig, um prävalente Wirbelkörperfrakturen zu erkennen. Beim Fehlen eines großen Traumas kann jede Fraktur bei Erwachsenen über dem Alter von 50 Jahren eine Diagnose von Osteoporose nahelegen, mit dem höchsten Risiko für eine nachfolgende Fraktur innerhalb einer kurzen Zeit nach der ersten Fraktur. BMD-Messungen mit DXA sind wichtig, um das individuelle Frakturrisiko besser abschätzen zu können. Eine grundlegende Laboruntersuchung ist obligatorisch, um verschiedene Formen der sekundären Osteoporose ausschließen zu können.Der DVO-Patientenfindungs-Algorithmus basiert auf dem Geschlecht, Alter, Knochenmineraldichte und vorbestehenden Frakturen als wichtigste Informationen. Die Indikation für eine aktive anti-osteoporotische Therapie kann durch multiple Risikofaktoren modifiziert und verfeinert werden. Dieser Algorithmus wurde seit dem Richtlinien-Update 2006 verwendet und wurde entsprechend der internationalen Literatur zu Risikofaktoren für Osteoporose und osteoporotische Frakturen aktualisiert und angepasst.Die Behandlung der Osteoporose enthält viele Therapiepfeiler. Zusammen mit Empfehlungen für Bewegung, Physiotherapie und Sturzprävention sowie Ernährung (z. B. Calcium, Vit. D), werden pharmakologische Behandlungen basierend auf evidenzbasierter Medizin empfohlen. Die aktiven Anti-Osteoporose-Medikamente müssen für die Indikation postmenopausale Osteoporose und männliche Osteoporose in Deutschland, Österreich und der Schweiz zugelassen sein. Das Management und die Vorbeugung von häufigen oder seltenen Nebenwirkungen aufgrund von Anti-Osteoporose-Behandlungen, die in der klinischen Praxis angewendet werden, werden ebenfalls detailliert behandelt.

A new species of tree snake Dipsadoboa montisilva Branch, Conradie & Tolley sp. nov. (Serpentes: Colubridae) is described from the ‘sky islands’ of Mount Mabu and Mount Ribáuè in northern Mozambique. Features of scalation, colour, body form and habitat distinguish the new species from other Dipsadoboa. This is supported by a phylogenetic analysis using one mitochondrial marker (cytochrome b) that shows the new Mozambican species is divergent from other sampled Dipsadoboa, including D. flavida and D. aulica, the only congeners known to occur in Mozambique. Morphologically, the new Dipsadoboa forms part of the D. werneri-shrevei complex from east and southeast Africa, but differs in having higher subcaudal counts, a different temporal pattern and only two supralabials entering the orbit. Phylogenetically, it occurs in a clade with D. shrevei and D. werneri. The status of D. shrevei in East Africa is reassessed, particularly in terms of the poorly-known Dipsadoboa shrevei kageleri from northern Tanzania. It is morphologically well defined from D. shrevei shrevei and utilises a different habitat. Although based on limited genetic data, it appears to be well-defined from typical D. shrevei and is accordingly raised to specific status. The only Tanzanian record for typical D. shrevei from Mtene, Rondo Plateau in southeast Tanzania is well isolated from the species’ range to the west (e.g. Zambia, Angola) and the published scalation features, particularly ventral counts, do not fully accord with D. shrevei. The Rondo Plateau population is treated as Dipsadoboa incerta sedis, and because we return D. shrevei to its binomial status, we can no longer consider D. shrevei as occurring in Tanzania. Biogeographically, the Rondo Plateau population may have a stronger affinity to the new Mozambican species. The discovery of isolated populations of the new species in mid-altitude forest remnants on Mt Mabu and Mt Ribáuè emphasizes the high conservation importance of the Mozambique forest ‘sky islands’ from which numerous other endemic new species have been recently discovered. These species are impacted by ongoing habitat destruction through slash and burn clearing for subsistence agriculture.

In December 2006, symptoms typical of iris yellow spot caused by Iris yellow spot virus (IYSV; genus Tospovirus, family Bunyaviridae) were observed on scapes (seed stalks) in an onion (Allium cepa L.) seed crop in the Klein Karoo of the Western Cape Province, South Africa. Symptoms included diamond-shaped chlorotic or necrotic lesions on the scapes, some of which had ‘green-islands’ with nested diamond-shaped lesions, as well as indistinct, circular to irregular, chlorotic or necrotic lesions of various sizes. At the time symptoms were observed, approximately 5% of the scapes had lodged as a result of extensive lesions resembling those caused by IYSV. The crop was 2 to 3 weeks from harvest. Symptomatic tissue from two plants (two samples from one plant and four samples from the other plant) was tested for IYSV by reverse-transcriptase (RT)-PCR. Total RNA was extracted from symptomatic scape tissue with the SV Total RNA Isolation System (Promega, Madison, WI) according to the manufacturer's instructions. First strand cDNA was synthesized with the RevertAid H Minus First Strand cDNA Synthesis kit (Fermentas Inc., Hanover, MD), followed by PCR amplification with primers IYSV-For (TGG YGG AGA TGY RGA TGT GGT) and IYSV-Rev (ATT YTT GGG TTT AGA AGA CTC ACC), which amplify the nucleocapsid (NP) gene of IYSV. An amplicon of expected size (approximately 750 bp) was observed for each of the symptomatic plants assayed and was sequenced. Comparison of the sequence (GenBank Accession No. EF579801) with GenBank sequences revealed 95% sequence identity with the NP gene of IYSV GenBank Accession No. EF419888, with eight amino acid differences. The known geographic distribution of IYSV in onion bulb or seed crops has increased rapidly in recent years in many areas of the world (1). To our knowledge, this is the first confirmation of IYSV in South Africa. Approximately 6,100 ha of onion bulb crops are grown annually in South Africa in the Western Cape, Kwazulu Natal, Limpopo, and Northern Cape provinces, and 600 ha of onion seed crops are grown primarily in the semi-arid regions of the Western Cape. Examination of an additional 10 onion seed crops in the Klein Karoo during January 2007 revealed the presence of iris yellow spot in three more crops at approximately 5% incidence in each crop. The four symptomatic crops had all been planted as bulb-to-seed crops, using vernalized bulbs produced on the same farm. This suggests that IYSV may have been disseminated into the seed crops on the vernalized bulbs, either as infected bulb tissue or in viruliferous thrips on the bulbs. Reference: (1) D. H. Gent et al. Plant Dis. 90:1468, 2006.

For many years phytoplasma diseases have caused serious losses in most of the major grape-growing regions of the world, except South Africa, where a mixed phytoplasma infection was first reported in 2006 (1). During the early growing season of 2006, symptoms consistent with phytoplasma disease were observed in vineyards in the Olifants River Valley. Symptoms included yellowing of leaves, incomplete lignification of shoots, shortening of internodes, and the abortion of growth tips and immature bunches. Symptomatic shoots and leaves from grapevine cultivars (Merlot, Shiraz, Cabernet Sauvignon, Ruby Cabernet, Pinotage, Corinth, Chardonnay, Columbar, Chenin blanc, Sauvignon blanc, Sultana, and Regal) were collected during the early growing season (November) of 2006, 2007, and 2008. Total DNA was extracted from 32 of these samples (from single plants in the same vineyards over the 3 years) with the Invisorb Spin Plant Mini Kit (Invitek, Berlin, Germany) and tested by nested PCR using two universal primer pairs, P1/P7 and R16F2n/R16R2 (3). The first round of PCR of the 2006 samples yielded 1.8-kb fragments for 17 of the samples, while the nested PCR yielded an additional seven positive samples, confirming the necessity of nested PCR for reliable diagnosis. A similar trend was observed in the 2007 and 2008 PCR test results. All asymptomatic plants, which were included as negative controls, and water controls were negative by nested PCR. Twenty-four 1,245-bp amplicons, generated by nested PCR, were excised from gels, purified with a NucleoSpin Extract II Kit (Macherey-Nagel, Düren, Germany) and directly sequenced. Sequence data was compiled with the BioEdit Version 7.0.4.1 sequence alignment editor software (2), aligned using ClustalW Version 1.4 (4), and a consensus sequence was generated (GenBank Accession No. GQ365729). A BLAST search of the NCBI GenBank database using the individual sequences revealed high sequence identities (≥99%) with the aster yellows phytoplasma group (16SrI) and specifically with the subgroup 16SrI-B. In a comparison of the sequences of the 1.2-kb PCR fragments of 24 local samples with each other, sequence identities of ~99% were observed. These results clearly illustrate that all vines screened were infected with the same phytoplasma. Single nucleotide differences observed between different isolates may indicate the presence of closely related sequence variants of this phytoplasma. Aster yellows occurs worldwide and has been reported to infect grapevine–South Africa can now be added to this list. During the three seasons of our study, the area in which symptomatic vineyards were observed increased significantly, indicating spread by a biological vector. Moreover, infected vineyards were noticed in two other South African grape-growing regions. In contrast to the previous report, which reported a mixed infection of phytoplasmas of groups 16SrXII-A and 16SrII-B (1), PCR screening and sequencing of more than 40 individual samples from these areas confirmed these all to be infected with aster yellows phytoplasma only. To our knowledge, this is the first report of the detection and identification of an aster yellows phytoplasma causing grapevine yellows disease in South Africa. References: (1) S. Botti and A. Bertaccini. Plant Dis. 90:1360, 2006. (2) T. A. Hall. Nucleic Acids. Symp. Ser. 41:95, 1999. (3) I.-M. Lee et al. Phytopathology 83:834, 1993. (4) J. D. Thompson et al. Nucleic Acids Res. 22:4673, 1994.

The African green and bush snakes of the genus Philothamnus currently comprises 21 species and three subspecies and occurs throughout sub-Saharan Africa. The genus has been the subject of previous taxonomic revisions based on traditional morphological characters and limited genetic assessment, and may not reflect their evolutionary history. Indeed, previous findings based on phylogenetics show discordant results of interspecific relationships and question the monophyly of the genus, although taxon sampling has been limited to date. We investigated phylogenetic affinities within Philothamnus with more inclusive genetic and geographical sampling, with the aim of better understanding their evolutionary history, so that future taxonomic revision of Philothamnus can be better informed. Species relationships were examined within a phylogenetic context and sampling included 133 ingroup samples from 16 taxa. Phylogenies were constructed in Bayesian and likelihood frameworks using three mitochondrial (16S, cyt b and ND4) and two nuclear (c-mos and RAG1) markers. Competing hypotheses relating to the monophyly of the genus were tested with a Shimodaira-Hasegawa test. To examine species boundaries, Bayesian General Mixed Yule-Coalescent Model and multi-rate Poisson Tree Processes analyses were conducted. In addition, a barcoding approach was used to further clarify species-level relationships by comparing frequency distributions between intra- and interspecific sequence divergence. The genus was recovered as monophyletic; however, species-delimitation results suggest that the current taxonomy does not reflect the evolutionary history of this group. For example, Philothamnus s. semivariegatus is paraphyletic, with at least four distinct clades. Philothamnus carinatus consists of two cryptic (sister) lineages from Central and West Africa that are deeply divergent, suggesting a long history of isolation between those regions. Furthermore, the subspecies P. n. natalensis and P. n. occidentalis show strong support for species-level divergence, which reflects their morphological and ecological differences. Accordingly, we elevate P. occidentalisnov. comb. to a full species. A fully informed taxonomic revision of these taxa will require additional morphological and ecological data for corroboration, but it seems that the morphological characters (e.g. scalation, dentition) used to describe these species to date are labile within and between species. This most likely has clouded our understanding of the species boundaries within the genus. Our phylogeny and species-delimitation analyses should provide a sounder framework for taxonomy, but may also prove useful toward understanding the morphological adaptations of these species to their respective habitats.

Globally, breast cancer continues to be a major concern in women's health. Lifestyle related risk factors, specifically excess adipose tissue (adiposity) has reached epidemic proportions and has been identified as a major risk factor in the development of breast cancer. Dysfunctional adipose tissue has evoked research focusing on its association with metabolic-related conditions, breast cancer risk and progression. Adipose dysfunction in coordination with immune cells and inflammation, are responsible for accelerated cell growth and survival of cancer cells. Recently, evidence also implicates adiposity as a potential risk factor for chemotherapy resistance. Chemotherapeutic agents have been shown to negatively impact adipose tissue. Since adipose tissue is a major storage site for fatty acids, it is not unlikely that these negative effects may disrupt adipose tissue homeostasis. It is therefore argued that fatty acid composition may be altered due to the chemotherapeutic pharmacokinetics, which in turn could have severe health related outcomes. The underlying molecular mechanisms elucidating the effects of fatty acid composition in adiposity-linked drug resistance are still unclear and under explored. This review focuses on the potential role of adiposity in breast cancer and specifically emphasizes the role of fatty acids in cancer progression and treatment resistance.

Pachydactylus is the most species-rich reptile genus in southern Africa. Most species are habitat specialists adapted to hyper-arid conditions of the Namibian and north-western South African xeric regions. Although a fair number of phylogenetic studies and taxonomic revisions have been published, some species still remain rather enigmatic. In the ten years since the taxonomic revision of the weberi group, some of the species have not been recorded and our knowledge on their distribution, phylogenetic affinities, or intraspecific variability is limited or non-existent. Pachydactylus goodi is one such species. In this study, we report a newly discovered population of P. goodi in the Richtersveld National Park, South Africa, which considerably extends the known range of the species. In addition, the results of our phylogenetic analyses indicate that P. goodi is paraphyletic with respect to P. atorquatus. Although there is a striking colour polymorphism observed between these two species, the level of genetic differentiation within the goodi-atorquatus clade is comparable with intraspecific variability observed in other Pachydactylus species. As a result of these findings, which are further supported by morphological similarity of the two species, we conclude that they represent a single species and synonymise P. goodi with P. atorquatus.

White sharks (Carcharodon carcharias) are apex predators that play an important role in the structure and stability of marine ecosystems. Despite their ecological importance and protected status, white sharks are still subject to lethal control to reduce the risk of shark bites for recreational water users. The Shark Spotters program, pioneered in Cape Town, South Africa, provides a non-lethal alternative for reducing the risk of human-shark conflict. In this study we assessed the efficacy of the Shark Spotters program in reducing overlap between water users and white sharks at two popular beaches in False Bay, South Africa. We investigated seasonal and diel patterns in water use and shark presence at each beach, and thereafter quantified the impact of different shark warnings from shark spotters on water user abundance. We also assessed the impact of a fatal shark incident on patterns of water use. Our results revealed striking diel and seasonal overlap between white sharks and water users at both beaches. Despite this, there was a low rate of shark-human incidents (0.5/annum) which we attribute partly to the success of the Shark Spotters program. Shark spotters use visual (coloured flags) and auditory (siren) cues to inform water users of risk associated with white shark presence in the surf zone. Our results showed that the highest risk category (denoted by a white flag and accompanying siren) caused a significant reduction in water user abundance; however the secondary risk category (denoted by a red flag with no siren) had no significant effect on water users. A fatal shark incident was shown to negatively impact the number of water users present for at least three months following the incident. Our results indicate that the Shark Spotters program effectively reduces spatial overlap between white sharks and water users when the risk of conflict is highest.

Preeclampsia (PE) is a pregnancy-related hypertensive disorder that affects 5-8% of all pregnancies worldwide. Placental microRNA (miRNA) expression is known to be dysregulated during PE which includes miR-210. However, the role of miR-210 in the development of PE is still unknown. We have previously demonstrated STAT6, a transcription factor, to be a direct target of miR-210. In addition, STAT6 modulates levels of IL-4, an anti-inflammatory cytokine which is known to be beneficial during pregnancy. Given that the STAT6/IL-4 pathway is important for normal pregnancy, we hypothesized that an overexpression of miR-210 in mice will contribute to PE-like symptoms by inhibiting the STAT6/IL-4 pathway. Systolic blood pressures (SBP) were measured using the tail-cuff method on both WT (C57Bl/6J) and miR-210 TG mice. The miR-210 TG mice exhibited increased SBP compared to the WT mice (WT: 95±2 mmHg, miR-210 TG: 115±2.4 mmHg, p

Preeclampsia (PE) is an obstetric complication that is diagnosed by hypertension and proteinuria at or after 20 weeks of gestation. PE is a multifactorial disease, but it is widely accepted that impaired proangiogenic factors such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and antiangiogenic factor such as soluble FMS-like tyrosine kinase-1 (sFlt1) or VEGF receptor-1 balance during pregnancy is linked to PE. sFlt1, a splice variant of Flt1 binds to either VEGF or PlGF and blocks their action. In addition, placental angiogenesis is known to be regulated by specific miRNAs that are typically dysregulated during PE highlighting the importance of these miRNAs in pregnancy disorders. miR-210 is upregulated in placentas and serum/plasma of PE women and is also known to modulate angiogenic pathways. Therefore, we hypothesized that miR-210 overexpression contributes to the development of PE-like symptoms by altering the angiogenic/antiangiogenic pathway. To this end, we demonstrate increased systolic blood pressure (SBP: miR-210 TG P = 115 ± 2 mm Hg vs. WT P = 95 ± 2 mm Hg, p

Background People at risk of developing rheumatoid arthritis (RA) may be candidates for interventions aimed at preventing RA development [1]. The identification of such “at risk” populations includes testing for genetic and other (e.g. autoantibody) biomarkers. However, little is known about the people9s perspectives on these tests, how they react and cope when identified as being a person “at risk” and what their unmet needs are. Objectives To expore the perceptions about RA and predictive testing and to understand the various reactions and coping strategies used when identified as being at risk of developing RA from the perspective of those directly concerned. Methods As part of the EuroTEAM project, a qualitative interview study with people who were informed of being at risk of developing RA was conducted. An interview schedule was developed and pilot-tested. Interviews were audio-recorded, transcribed verbatim and analyzed using thematic analysis. Results A total of 34 individuals (with rheumatoid factor and/or ACPA positive) already informed of being at risk of developing RA participated in the study, from Austria (n=15), Germany (n=15), and the UK (n=4). In Vienna, people who had been tested within an expanded health exam participated in this study. In Birmingham and Erlangen, people with arthralgia were recruited from the outpatient clinics. Analysis of the interview data revealed five overarching themes related to predictive testing in the context of RA (Figure). There were differences between the perceptions of althralgia patients and asymptomatic individuals. People suffering from pain were much more frightened and worried when informed of being at risk of developing RA. As a consequence, they modified their lives in a larger extent and had greater knowledge about RA than those without any symptoms who were rather surprised, kept calm and hardly changed their lifestyle after being tested positive. Allmost all participants in this study would appreciate precise predictive tests in the context of RA. However, more than half of them would refuse synovial biopsy (even if this could help quantify risk more accurately) or preventive medication. Recommendations for an improved procedure of predictive testing in the field of RA were given, which could promote uptake of preventive strategies. Conclusions Participants showed large differences in views about predictive testing in the context of RA risk and offered specific suggestions that should be incorporated into service design and delivery in the context of future predictive testing programmes. These findings may also be relevant to prediction and prevention in the context of other diseases where multiple genetic risk factors interact with environmental risk factors to drive disease development. References van Steenbergen, H.W., T.W. Huizinga, and A.H. van der Helm-van Mil, The preclinical phase of rheumatoid arthritis: what is acknowledged and what needs to be assessed? Arthritis Rheum, 2013. 65(9): p. 2219–32. Disclosure of Interest None declared

Demographic characteristics of included and excluded cases in the analysis. The proportion of males (50.4%) and females (49.6%) excluded were significantly different from those males (55%) and females (45%) included in the study. The proportions in each age group for cases included and excluded in the analysis were similar except for: 25-34 (29.3% vs 31.3%); 35-44 (28.5% vs 27.7%) and â Ľ65 (3% vs 3.7%) (95% CI for proportions overlap see Additional file 1). (DOCX 13Â kb)

Objective. Cross-cultural translation of patient-reported outcome measures (PROMs) is a lengthy process, often performed professionally. Cognitive interviewing assesses patient comprehension of PROMs. The objective was to evaluate the usefulness of cognitive interviewing to assess translations and compare professional (full) with non-professional (simplified) translation processes. Methods. A full protocol used for the Bristol RA Fatigue Multi-dimensional Questionnaire and Numerical Rating Scale (BRAF-MDQ, BRAF-NRS) was compared with a simplified protocol used for the RA Impact of Disease scale (RAID). RA patients in the UK, France, the Netherlands, Germany, Spain and Sweden completed the PROMs during cognitive interviewing (BRAFs in the UK were omitted as these were performed during development). Transcripts were deductively analysed for understanding, information retrieval, judgement and response options. Usefulness of cognitive interviewing was assessed by the nature of problems identified, and translation processes by percentage of consistently problematic items (⩾40% patients per country with similar concerns). Results. Sixty patients participated (72% women). For the BRAFs (full protocol) one problematic item was identified (of 23 items × 5 languages, 1/115 = 0.9%). For the RAID (simplified protocol) two problematic items were identified (of 7 items × 6 languages, 2/42 = 4.8%), of which one was revised (Dutch). Coping questions were problematic in both PROMs. Conclusion. Conceptual and cultural challenges though rare were important, as identified by formal evaluation, demonstrating that cognitive interviewing is crucial in PROM translations. Proportionately fewer problematic items were found for the full than for the simplified translation procedure, suggesting that while both are acceptable, professional PROM translation might be preferable. Coping may be a particularly challenging notion cross-culturally.

In recent years, an increasing amount of literature is emerging on candidate urine and blood-based biomarkers associated with incidence and severity of preeclampsia (PE) in pregnant women. While enthusiasm on the usefulness of several of these markers in predicting PE is evolving, essentially all work so far has focused on the needs of high-resource settings and high-income countries, resulting primarily in multi-parameter laboratory assays based on proteomic and metabolomics analysis techniques. These highly complex methods, however, require laboratory capabilities that are rarely available or affordable in low-resource settings (LRS). The importance of quantifying maternal and perinatal risks and identifying which pregnancies can be safely prolonged is also much greater in LRS, where intensive care facilities that can rapidly respond to PE-related health threats for women and infants are limited. For these reasons, simple, low cost, sensitive, and specific point-of-care (POC) tests are needed that can be performed by antenatal health care providers in LRS and that can facilitate decisions about detection and management of PE. Our study aims to provide a comprehensive systematic review of current and emerging blood and urine biomarkers for PE, not only on the basis of their clinical performance, but also of their suitability to be used in LRS-compatible test formats, such as lateral flow and other variants of POC rapid assays.

Despite the advances in therapies such as chemotherapy and radiotherapy, tumours have been shown to be resistant to the treatments. Gold nanoparticles (AuNPs) have been recognized as effective radiosensitizers of low energy (e.g. 200–500 kV) X-rays, leading to the emission of Auger electrons that cause highly localised ionizing damage to cells. Spherical AuNPs were synthesised via the reduction of the chloroaurate ions by sodium citrate. Characterisation of AuNPs involved UV-visible spectrophotometry, zeta (Z) potential, dynamic light scattering (DLS) and polydispersity index (PDI) measurements for determination of surface plasmon resonance (SPR), surface charge and stability, as well as transmission electron microscopy (TEM) for hydrodynamic core sizes, size distribution width and shape of AuNPs. Both the 5 and 10 nm AuNPs were found to be anionic with λmax absorbance of 525 nm and uniform size distribution. DLS measurement at 38.12 nm and 48.50 nm, respectively for 5 nm and 10 nm AuNPs, points to aggregation of the AuNPs. However, TEM measurements confirmed the core size of the 10 nm AuNPs. Non-malignant Chinese hamster ovary (CHO-K1), brain endothelial (BEnd5), breast (MCF-10A), isolated human lymphocytes and malignant breast (MCF-7) cell lines were treated with 50 μg/ml of AuNPs, and irradiated with either 1, 2 or 4 Gy X-rays or 1 or 2 Gy p(66)/Be neutron radiation. The γ-H2AX foci assay, cytokinesis-block micronucleus assay, MTT assay and fluorescence-activated cell sorting (FACS) was used to determine that amount of double stranded breaks (DSBs) in isolated lymphocytes, the presence and number of micronuclei (MNi) within binucleated cells (BNCs), cell viability and cell cycle progression, respectively. Preliminary experiments that established the reliability of the study regarding the induction of DNA damage after the bombardment of AuNPs by scattered low kV X-rays, were carried out on lymphocytes. Combined treatment (AuNPs and radiation) resulted in more endogenous foci in comparison to lymphocytes that were treated with AuNPs only. The CHO-K1 and MCF-7 cells showed higher MNi frequencies after the combination treatment of AuNPs and radiation compared to the number of MNi in samples exposed to AuNPs and radiation separately. The AuNPs alone influenced the cellular kinetics of all cell types. Interaction indices, which is the enhancement factor of AuNPs in combination with radiation, for AuNPs and 6 MV 2 Gy X-rays of 1.6 to 1.7 and 1.3 to 1.4 have respectively been determined for CHO-K1 and MCF-7 cells, whilst that for the other cell types used in the study were not different from Unity. As expected, the interaction indices between AuNPs and p(66)/Be neutrons was lower than the interaction indices after 2 Gy X-rays, as p(66)/Be neutrons interact only with the nuclei of the AuNP's atoms and the X-ray photons interact with the orbital electrons of the atoms of the AuNPs leading to Auger electron emission. The cell viability assay showed that 50 μg/ml of AuNPs had an inhibitory effect on cellular…

Background BRAF-NRS are a trio of items for fatigue severity, impact and coping. At development, patients wanted the NRS-Severity & Impact anchors to read 0=No fatigue/effect, 10=Totally exhausted/Great deal of effect, but the NRS-Coping to read 0=Not at all well, 10=Very well. 1 Construct and criterion validity of the NRS-Coping-NRS are less strong than NRS-Severity and Impact; 2 cognitive interviewing shows patient confusion over Coping anchors. 3 Objectives Test construct and criterion validity of BRAF-NRS V2, which has Revised NRS-Coping anchors of 0=Very well, 10=Not at all well (NRS-Severity and Impact unchanged), in 6 EU countries. Methods RA patients from France, Germany, Netherlands, Spain, Sweden and UK completed the BRAF-NRS V2 Revised, BRAF-NRS Original, BRAF-MDQ, RAID, SF-36. Spearman9s correlations assessed criterion and construct validity. Results Of 1276 patients 76% were female, median HAQ 1.0 (IQR 0.375–1.5). Mean BRAF-NRS-Coping Revised 4.0 (SD 2.66) vs Original 5.95 (SD 2.57), NRS-Severity 4.86 (SD 2.56), NRS-Impact 4.61 (SD 2.69). BRAF-NRS-Severity and Impact had appropriate validity with all 18 variables, overall and by country (r=0.46–0.96). Table shows BRAF-NRS-Coping Revised had better validity than NRS-Coping Original in all variables overall (stronger correlations bolded), and for 15–18/18 variables in all countrie except Spain (3/18). The difference in strength of correlations between the versions was large for the total sample, but minimal for Spain. Conclusions BRAF-NRS V2 Revised has construct and criterion validity across 6 EU countries. Whilst the BRAF-NRS-Coping Original is acceptable, the BRAF-NRS-Coping Revised has greater validity. In Spain, the validity of both versions is lower but similar to each other. Further exploration of the concept and wording of “coping” in the Spanish population is warranted. References Nicklin et al 2010a; Nicklin et al 2010b; Hewlett et al 2016 in press Acknowledgement EULAR project grant EP1009 Disclosure of Interest None declared

Background Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are rare but diagnostically challenging clinical problems. Because of the abundance of differential diagnoses, a generally accepted diagnostic guideline has not yet been established. Besides a thorough medical history, physical examination, and laboratory testing, imaging techniques are important tools in the diagnostic workup of FUO and IUO. In the last few years, 18F-FDG-PET/CT has been found to be a suitable diagnostic tool for FUO/IUO, as it is able to detect inflammatory and malignant processes with a high spatial resolution. Objectives The present study is carried out at to quantify the utility of 18F-FDG-PET/CT for the diagnosis of FUO and IUO. The study, moreover, evaluates special clinical markers, that increase the possibility of diagnosing FUO or IUO with a 18F-FDG-PET/CT. Methods All patients presenting with FUO or IUO at the University Clinic of Erlangen between 2007 and 2015 were clinically documented and subjected to 18F-FDG-PET/CT scanning. 18F-FDG-PET/CT scans were considered positive when a focal uptake of the tracer was detected additionally to the standard areas of physiological tracer uptake. 18F-FDG-PET/CT results were compared to the final diagnosis and classified as helpful or non-helpful in establishing the final diagnosis. Multivariate logistic regression was used to identify clinical parameters that correlated with a helpful 18F-FDG-PET/CT in patients with and without FUO as well as in patients with and without IUO. Results Of the 240 patients enrolled 72 presented with FUO, 142 with IUO and 26 did not fulfill FUO or IUO criteria. 235 patients were included in the multivariate logistic regression model. Final diagnosis was established in 190 patients (79.2%). In 136 (56.7% of all patients and 71.6% of the patients with a diagnosis), the 18F-FDG-PET/CT was helpful in finding the diagnosis. The chance was higher in patients without fever (p=0.003), those aged >50 years (p=0.002; p=0.005, respectively) and those with a CRP level >30 mg/dl (p=0.003; p=0.008, respectively). Conclusions Our study shows that if the standard diagnostic tests (laboratory, chest x-ray and abdominal ultrasound) did not identify the cause of FUO/IUO, 18F-FDG-PET/CT scanning should be applied in the early stage of the diagnostic process. An early use of an 18F-FDG-PET/CT is especially helpful to establish a final diagnosis in patients with an elevated C-reactive protein and age over 50 years. Disclosure of Interest None declared

Background The BRAF-MDQ1,2 and RAID3 are patient-reported outcome measures derived from the patient perspective. The 20 item BRAF-MDQ has 4 factors (physical, cognitive, emotional fatigue, living with fatigue) and the 7 item RAID is uni-dimensional. The BRAF-MDQ properties have not been tested outside the UK, nor the validity of the new Swedish RAID examined. Objectives To test the structure, construct and criterion validity of the BRAF-MDQ and the RAID in 6 EU countries. Methods Survey of RA clinic patients in clinics in France, Germany, Netherlands, Spain, Sweden and UK (F, G, N, Sp, Sw, UK), using BRAF-MDQ, RAID and SF-36. Factor structure examined by Confirmatory Factor Analysis and internal consistency by Cronbach9s Alpha. Criterion validity for the BRAF-MDQ evaluated by internal Spearman9s correlations, and for BRAF-MDQ and RAID fatigue item by correlation with each other and SF-36 Vitality subscale. Construct validity of BRAF-MDQ and RAID evaluated by Spearman9s Correlation with each other, HAQ, and SF-36 domains. Analysis conducted overall and by individual country and for BRAF-MDQ by total and subscales. Results 1276 patients participated: F 206, G 216, N 317, Sp 157, Sw 170, UK 210. Disease duration Confirmatory factor analysis: BRAF-MDQ original UK 4 factor structure was confirmed in each country, demonstrating one factor for each set of variables, with high factor loadings (0.71–0.96). Bootstrapping (4 sets of analyses on 20 random samples of 50% of patients/country), found the structure held true in at least 19/20 sets per country. RAID single factor structure was confirmed in all countries (0.75–0.95). Internal consistency ranged from 0.75–0.96 for the BRAF-MDQ (total and subscales) and the RAID ranged from 0.93–0.96 (overall and by country). Criterion validity overall and by country: The BRAF-MDQ correlated internally and with the SF-36 Vitality and RAID fatigue items (0.6–0.93). Construct validity: BRAF-MDQ and RAID correlatied with each other, the HAQ, and remaining 8 SF36 domains (0.46–0.86). Conclusions The BRAF-MDQ and RAID demonstrate strong, consistent factor structure and internal consistency, with moderate-good criterion and construct validity across 6 EU countries, reflecting their robust methods of development. This indicates no specific country scoring is necessary, and strengthens the case for measuring both fatigue and impact in multi-country studies. References Nicklin et al, Arth Care Res 2010:62:1552–8. Nicklin et al, Arth Care Res 2010:62:1559–6. Gossec et al, Ann Rheum Dis 2009;68:1680–5 Acknowledgement EULAR project grant EP1009 Disclosure of Interest None declared