Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae.

A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation. RNA interference-mediated silencing of Ty expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington's disease model, and expanded the replicative lifespan of yeast in a partially Hsp104-dependent manner. The results are in line with recent data demonstrating that VLPs might act as aging factors in mammals, including humans, and extend these findings by linking VLPs to a toxic accumulation of protein aggregates and raising the possibility that they might negatively influence neurological disease progression.

Promising functional outcomes following anterior cruciate ligament repair with suture augmentation.

PURPOSE: There has been a renewed interest in the repair of the torn anterior cruciate ligament (ACL). Purpose of this study was to evaluate the functional outcome of arthroscopic ACL repair with additional suture augmentation (SA), hypothesizing that isolated ACL ruptures would yield superior patient-reported outcome measures (PROMs) compared to those with concomitant meniscal and/or ligamentous injuries. METHODS: This is a retrospective analysis of 93 consecutive patients (67 female, median age 42 years) who underwent arthroscopic ACL repair with SA between January 2017 and March 2019 for an acute traumatic ACL tear confirmed by magnetic resonance imaging (MRI). Patients with pre- or intraoperative mid-substance or distal ACL tears and/or poor tissue quality of the ACL remnant were not considered for ACL repair but were scheduled for an ACL reconstruction with a tendon autograft. In patients who underwent ACL repair with SA, the SA construct was proximally stabilized with a flip-button and distally with a suture anchor. Surgery was preferably performed on the day of injury and all surgeries were performed by the same surgeon. Postoperative rehabilitation included partial weight-bearing (20 kg) for 6 weeks and immobilization in a brace limited at 90-degrees of knee flexion for 4 weeks. Patient-reported outcome measures (PROMs) were determined using International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Lysholm Score (LS), Tegner Activity Score (TS) and Forgotten Joint Score (FJS). Knee-laxity was assessed using the KT-1000 arthrometer (Med Metrics Corp. Inc., San Diego, USA). RESULTS: Nine patients underwent revision surgery for a traumatic re-tear (four patients) and chronic instability (five patients) and were excluded from further functional analysis. Functional results of 77 patients (54 female) with a median age of 44 years (IQR 33-51) on the day of surgery were available for follow-up after a median time of 35 months (IQR 33-44). Concomitant injuries were observed in 66 Patients (86%), meniscal injuries in 43 patients (55%) and ligamentous injuries in 50 patients (65%). Median interval from injury to surgery was 1 day (IQR 0-1) with 81% (62/77) of patients being treated within 24 h of injury. The median IKDC was 92 (IQR 86-99), the median LS was 95 (IQR 86-100), the median pre-traumatic TS was 7 (IQR 6-7), the median post-traumatic TS was 6 (IQR 5-7) with a non-significant median difference (TSDiff) of 0 (IQR 0-1). The median FJS was 95 (IQR 78-98). KT-1000 measurements were available in 34 of 77 patients with a median postoperative laxity compared to the uninjured side of 1 mm (IQR 0-2). Interval from injury to surgery, patients' age, body mass index (BMI), knee laxity and concomitant ligamentous or meniscal injuries had no statistically significant impact on postoperative PROMs (n.s.). CONCLUSION: Following arthroscopic ACL repair with SA good-to-excellent functional results were observed. However, a failure rate of 10% cannot be neglected and warrants further attention. Concomitant injuries to the meniscus and/or collateral ligaments do not seem to be associated with inferior PROMs. LEVEL OF EVIDENCE: Level IV.

[Characteristic values and test statistical goodness of the Veterans RAND 12-Item Health Survey (VR-12) in patients with chronic pain : An evaluation based on the KEDOQ pain dataset]. / Kennwerte und teststatistische Güte des Veterans RAND 12-Item Health Survey (VR-12) bei Patienten mit chronischem Schmerz : Eine Auswertung auf Basis des KEDOQ-Schmerz-Datensatzes.

The Veterans RAND 12-Item Health Survey (VR-12) was added to the German Pain Questionnaire (DSF) as a self-report measure of health-related quality of life in 2016, replacing the previously used SF-12, which required a license. Both measures have 12 items and include a physical component summary (PCS) and a mental component summary (MCS). Evaluations with a larger sample on characteristic values and on the test-statistical goodness of the VR-12 in patients with chronic pain are so far missing. Data on the VR-12 and other procedures of the DSF were evaluated from 11,644 patients from 31 centers participating in KEDOQ pain. The patients filled out the DSF before starting a pain therapy treatment. Change sensitivity was determined for 565 patients for whom the VR-12 was available from a follow-up questionnaire of the DSF several months after the initial survey.The reliability (Cronbach's alpha) of the PCS was rtt = 0.78 and for the MCS rtt = 0.84. The MCS had significant relationships with the depression, anxiety and stress scales (r = -0.51 to r = -0.72), and the PCS correlated more highly with areas of pain-related impairment (r = -0.48 to r = -0.52). Patients with higher pain chronicity, those with higher pain severity, and those with evidence of high psychological distress described significantly lower health-related quality of life in PCS and MCS. The effect size (ES) of change in terms of improvement in health-related quality of life was ES = 0.33 in the MCS and ES = 0.51 in the PCS.The results are in agreement with the findings of the SF-36 and SF-12 in patient collectives with chronic pain. In summary, they show that the VR-12 is an adequate substitute for the SF-12 in the German pain questionnaire.

Influence of soil microbes on Escherichia coli O157:H7 survival in soil rinse and artificial soil.

AIMS: This research investigated the influence of soil microbiota on Escherichia coli O157:H7 survival in soil rinse and artificial soil. Additionally, the influence of selected soil bacteria on E. coli O157:H7 in soil environments was determined. METHODS AND RESULTS: Escherichia coli O157:H7 counts (log CFU per ml or g-1 ) were determined by spread plating: (i) artificial soil amended with soil rinse (filter-sterilized and unfiltered) at 30°C; (ii) unfiltered soil rinse (50 ml) treated with cycloheximide (200 µg ml-1 ), vancomycin (40 µg ml-1 ), heat (80°C, 15 min) and no treatment (control) for 7 days at 30°C and (iii) filtered soil rinse with selected soil bacterial isolates over 7 days. There was a significant difference (P = 0·027) in E. coli O157:H7 counts after 35 days between artificial soils amended with filtered (4·45 ± 0·29) and non-filtered (1·83 ± 0·33) soil rinse. There were significant differences (P < 0·05) in E. coli O157:H7 counts after 3 days of incubation between soil rinse treatments (heat (7·04 ± 0·03), cycloheximide (6·94 ± 0·05), vancomycin (4·26 ± 0·98) and control (5·00 ± 0·93)). Lastly, a significant difference (P < 0·05) in E. coli O157:H7 counts was observed after 3 days of incubation at 30°C in filtered soil rinse when incubated with Paenibacillus alvei versus other soil bacterial isolates evaluated. CONCLUSIONS: Soil microbiota isolated from Florida sandy soil influenced E. coli O157:H7 survival. Specifically, P. alvei reduced E. coli O157:H7 by over 3 log CFU per ml after 3 days of incubation at 30°C in filtered soil rinse. SIGNIFICANCE AND IMPACT OF THE STUDY: This research identified soil bacterial isolates that may reduce E. coli O157:H7 in the soil environment and be used in future biocontrol applications.

Escherichia coli O157 survival in liquid culture and artificial soil microcosms with variable pH, humic acid and clay content.

AIMS: This research was performed to investigate the influence of clay and humic acid on Escherichia coli O157 survival in model soils. Additionally, the influence of pH and humic acid on E. coli O157 in liquid culture was investigated. METHODS AND RESULTS: Artificial soil microcosms were prepared with sand, kaolinite, bentonite and humic acid. Artificial soil microcosms pH was adjusted (6·0-7·0) with aluminium sulphate before E. coli O157 inoculation. After 56 days of incubation at 30°C, significant differences in E. coli O157 log CFU per gram were observed between 0 and 1000 ppm (P < 0·0001) and 0 and 5000 ppm (P < 0·0001) humic acid in 1·5% clay soils, but not in 7·5 or 15% clay soils. Significant differences (P < 0·05) in E. coli O157 log CFU per ml were observed in liquid culture influenced by humic acid concentrations after 8 h at 37°C. CONCLUSIONS: The developed model soils support E. coli O157 populations over 28 days, and higher clay soils may aid in E. coli O157 survival. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide insights into physicochemical properties of soil that may influence E. coli O157 in the environment and help explain E. coli O157 survival in various soils and geographical regions.

Evaluating the Vestibulo-Ocular Reflex Following Traumatic Brain Injury: A Scoping Review.

Purpose:To identify the tests and tools used to evaluate vestibulo-ocular reflex (VOR) function after traumatic brain injury (TBI) in all age groups and across TBI severity.Methods: An electronic search was conducted to include relevant peer-reviewed literature published up to November 2019. Studies included those done with humans, of all ages, and had assessments of oculomotor and/or vestibulo-ocular function in TBI.Results: Of the articles selected (N = 48), 50% were published in 2018/2019. A majority targeted mild TBI, with equal focus on non-computerized versus computerized measures of VOR. Computerized assessment tools used were videonystagmography, dynamic visual acuity/gaze stability, rotary chair, and caloric irrigation. Non-computerized tests included the head thrust, dynamic visual acuity, gaze stability, head shaking nystagmus, rotary chair tests and the vestibular/oculomotor screening tool. High variability in administration protocols were identified. Namely: testing environment, distances/positioning/equipment used, active/passive state, procedures, rotation frequencies, and variables observed.Conclusions: There is a rapid growth of literature incorporating VOR tests in mild TBI but moderate and severe TBI continues to be under-represented. Determining how to pair a clinical test with a computerized tool and developing standardized protocols when administering tests will help in developing an optimal battery assessing the VOR in TBI.

Assessing the spreading potential of an undetected case of COVID-19 in orthopaedic surgery.

BACKGROUND: With the novel coronavirus-induced disease (COVID-19), there is the fear of nosocomial infections and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions to healthcare workers (HCW). We report the case of a 64-year-old male patient who underwent explantation of a shoulder prosthesis due to a periprosthetic infection. He was tested SARS-CoV-2 positive 7 days after admission to the orthopaedic department following strict infection control measures, routinely including screening all patients for multi-drug-resistant organism (MDRO) colonization upon admission. Aim of our study is to report on the spreading potential of SARS-CoV-2 in a healthcare setting if standard contact precautions and infection control measures have been established. METHODS: All HCW with exposure to the patient from day of admission until confirmed diagnosis of COVID-19 were identified and underwent oropharyngeal swab testing for SARS-CoV-2 by real-time RT-PCR. RESULTS: Sixty-six HCW were identified: nine orthopaedic surgeons, four anaesthesiologists, 25 orthopaedic nurses, five nurse anesthetists, eight scrub nurses, five nursing students, two medical assistants and seven service employees. Fourteen HCW (21%) showed clinical symptoms compatible with a SARS-CoV-2 infection: cough (n = 4), sore throat (n = 3), nasal congestion (n = 3), dyspnea (n = 2), fever (n = 1), headache and myalgia (n = 1). SARS-CoV-2 was not detected in any of the 66 HCW. CONCLUSION: Hygienic measures and contact precautions, aimed at preventing the spread of MRDO, may have helped to prevent a SARS-CoV-2 transmission to HCW-despite high-risk exposure during intubation, surgical treatment and general care. LEVEL OF EVIDENCE: IV, case series.

Brachial plexitis or neuritis? MRI features of lesion distribution in Parsonage-Turner syndrome.

INTRODUCTION: This study seeks to characterize lesion distribution in Parsonage-Turner Syndrome (PTS) using high-resolution MRI. METHODS: MRIs of 27 patients with clinically confirmed PTS were reviewed. Two radiologists independently evaluated the brachial plexus proper, side and terminal plexus branches, and more distal, upper extremity nerves. RESULTS: All patients had at least 1 clinically involved nerve. MRI revealed that the plexus appeared normal in 24 of 27 patients; in 3 other patients, signal hyperintensity was seen immediately proximal to the take-off of abnormal side or terminal branch nerves. Focal intrinsic constrictions were detected in 32 of 38 nerves. MRI interobserver agreement was high (Cohen's κ = 0.839). DISCUSSION: MRI findings, corroborated by electrodiagnostic testing, localized abnormalities to plexus branches and peripheral nerves, suggesting that PTS is characterized by 1 or more mononeuropathies rather than changes involving a portion of or the complete plexus proper. These results may improve diagnosis, prognostication, and management. Muscle Nerve 58: 359-366, 2018.

Influence of gestational diabetes on fetal autonomic nervous system: a study using phase-rectified signal-averaging analysis.

OBJECTIVES: Maternal gestational diabetes mellitus (GDM) is known to influence fetal physiology. Phase-rectified signal averaging (PRSA) is an innovative signal-processing technique that can be used to investigate fetal heart signals. The PRSA-calculated variables average acceleration capacity (AAC) and average deceleration capacity (ADC) are established indices of autonomic nervous system (ANS) function. The aim of this study was to evaluate the influence of GDM on the fetal cardiovascular and ANS function in human pregnancy using PRSA. METHODS: This was a prospective clinical case-control study of 58 mothers with diagnosed GDM and 58 gestational-age matched healthy controls in the third trimester of pregnancy. Fetal cardiotocography (CTG) recordings were performed in all cases at entry to the study, and a follow-up recording was performed in 19 GDM cases close to delivery. The AAC and ADC indices were calculated by the PRSA method and fetal heart rate short-term variation (STV) by CTG software according to Dawes-Redman criteria. RESULTS: Mean gestational age of both groups at study entry was 35.7 weeks. There was a significant difference in mean AAC (1.97 ± 0.33 bpm vs 2.42 ± 0.57 bpm; P < 0.001) and ADC (1.94 ± 0.32 bpm vs 2.28 ± 0.46 bpm; P < 0.001) between controls and fetuses of diabetic mothers. This difference could not be demonstrated using standard computerized fetal CTG analysis of STV (controls, 10.8 ± 3.0 ms vs GDM group, 11.3 ± 2.5 ms; P = 0.32). Longitudinal fetal heart rate measurements in a subgroup of women with diabetes were not significantly different from those at study entry. CONCLUSIONS: Our findings show increased ANS activity in fetuses of diabetic mothers in late gestation. Analysis of human fetal cardiovascular and ANS function by PRSA may offer improved surveillance over conventional techniques linking GDM pregnancy to future cardiovascular dysfunction in the offspring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[Specific characteristics of chest X­ray in childhood : Basics for radiologists]. / Besonderheiten des Röntgen-Thorax im Kindesalter : Was Radiologen wissen sollten.

The radiographic technique of pediatric chest X­rays is substantially different from that in adults. In nearly all cases ap/pa X­rays are sufficient and lateral radiographs are rarely needed. In the first years of life the thymus may overshadow the heart, the great vessels and the lung hila. The most important anatomical structures essential for diagnosing pathological findings of the lungs and mediastinum are the trachea with the bifurcation and the main bronchi with the adjacent great vessels. For the assessment of distended lungs and intrathoracic consolidations, fundamental knowledge of the anatomy in childhood and malformations which can involve the airways, the lungs, the heart, as well as systemic and pulmonary vessels are indispensable. Diseases of the pleura and the chest wall should always be investigated by ultrasound. Malignant disorders are rare in children, except for lymphomas. Optimized computed tomography (CT) and/or magnetic resonance imaging (MRI) are crucial in the diagnostic workflow of complex congenital heart diseases, complex lung and airway malformations, pulmonary complications in cystic fibrosis and the diagnostics of all tumors in order to make the right treatment decisions.

Longitudinal study of computerized cardiotocography in early fetal growth restriction.

OBJECTIVES: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome. METHODS: The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety-net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2-year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety-net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2-year infant outcome. RESULTS: One hundred and forty-nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut-off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2-7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety-net criteria) was 5% (IQR, 4-7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth-weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short- or long-term infant outcomes. CONCLUSION: The TRUFFLE study showed that a strategy of DV monitoring with safety-net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2-year infant survival without neurological impairment. This post-hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety-net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV-PI is within normal range. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

How to monitor pregnancies complicated by fetal growth restriction and delivery before 32 weeks: post-hoc analysis of TRUFFLE study.

OBJECTIVES: In the recent TRUFFLE study, it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks' gestation, monitoring of the fetal ductus venosus (DV) waveform combined with computed cardiotocography (CTG) to determine timing of delivery increased the chance of infant survival without neurological impairment. However, concerns with the interpretation were raised, as DV monitoring appeared to be associated with a non-significant increase in fetal death, and some infants were delivered after 32 weeks, at which time the study protocol no longer applied. This secondary sensitivity analysis of the TRUFFLE study focuses on women who delivered before 32 completed weeks' gestation and analyzes in detail the cases of fetal death. METHODS: Monitoring data of 317 pregnancies with FGR that delivered before 32 weeks were analyzed, excluding those with absent outcome data or inevitable perinatal death. Women were allocated randomly to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate short-term variation (STV) on CTG; (2) early changes in fetal DV waveform; and (3) late changes in fetal DV waveform. Primary outcome was 2-year survival without neurological impairment. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. RESULTS: Two-year survival without neurological impairment occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however, the difference was not statistically significant (P = 0.21). Among the surviving infants in the DV groups, 93% were free of neurological impairment vs 85% of surviving infants in the CTG-STV group (P = 0.049). All fetal deaths (n = 7) occurred in the groups with DV monitoring. Of the monitoring parameters obtained shortly before fetal death in these seven cases, an abnormal CTG was observed in only one case. Multivariable regression analysis of factors at study entry demonstrated that a later gestational age, higher estimated fetal weight-to-50th percentile ratio and lower umbilical artery pulsatility index (PI)/fetal middle cerebral artery-PI ratio were significantly associated with normal outcome. Allocation to DV monitoring had a smaller effect on outcome, but remained in the model (P < 0.1). Abnormal fetal arterial Doppler before delivery was significantly associated with adverse outcome in the CTG-STV group. In contrast, abnormal DV flow was the only monitoring parameter associated with adverse outcome in the DV groups, while fetal arterial Doppler, STV below the cut-off used in the CTG-STV group and recurrent decelerations in fetal heart rate were not. CONCLUSIONS: In accordance with the findings of the TRUFFLE study on monitoring and intervention management of very preterm FGR, we found that the proportion of infants surviving without neuroimpairment was not significantly different when the decision for delivery was based on changes in DV waveform vs reduced STV on CTG. The uneven distribution of fetal deaths towards the DV groups was probably a chance effect, and neurological outcome was better among surviving children in these groups. Before 32 weeks, delaying delivery until abnormalities in DV-PI or STV and/or recurrent decelerations in fetal heat rate occur, as defined by the study protocol, is likely to be safe and possibly benefits long-term outcome. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Spontaneous polyploidy, gynogenesis and androgenesis in second generation (F2 ) koi Cyprinus carpio × goldfish Carassius auratus hybrids.

The objective of this study was to characterize the genetics of second generation (F2 ) koi Cyprinus carpio × goldfish Carassius auratus hybrids. Spermatozoa produced by a novel, fertile F1 male were found to be diploid by flow-cytometric analysis. Backcross (F1 female × C. carpio male and C. carpio female × F1 male) juveniles were triploid, confirming that female and male F1 hybrids both produced diploid gametes. The vast majority of surviving F2 juveniles was diploid and small proportions were aneuploid (2·1n-2·3n and 3·1n-3·9n), triploid (3n) and tetraploid (4n). Microsatellite genotyping showed that F2 diploids repeated either the complete maternal or the complete paternal genotype. Fish with the maternal genotype were female and fish with the paternal genotype were male. This demonstrates that F2 diploids were the result of spontaneous gynogenesis and spontaneous androgenesis. Analysis of microsatellite inheritance and the sex ratio in F2 crosses showed that spontaneous gynogenesis and androgenesis did not always occur in equal proportions. One cross was found to have an approximate equal number of androgenetic and gynogenetic offspring while in several other crosses spontaneous androgenesis was found to occur more frequently than spontaneous gynogenesis.

2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial.

BACKGROUND: No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV). METHODS: In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [<10th percentile] and a high umbilical artery Doppler pulsatility index [>95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age (<29 weeks vs ≥29 weeks), to three timing of delivery plans, which differed according to antenatal monitoring strategies: reduced cardiotocograph fetal heart rate STV (CTG STV), early DV changes (pulsatility index >95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499. FINDINGS: Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 29·1-32·1) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 140, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality. INTERPRETATION: Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age. FUNDING: ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany.

Bumblebee Flight in Heavy Turbulence.

High-resolution numerical simulations of a tethered model bumblebee in forward flight are performed superimposing homogeneous isotropic turbulent fluctuations to the uniform inflow. Despite tremendous variation in turbulence intensity, between 17% and 99% with respect to the mean flow, we do not find significant changes in cycle-averaged aerodynamic forces, moments, or flight power when averaged over realizations, compared to laminar inflow conditions. The variance of aerodynamic measures, however, significantly increases with increasing turbulence intensity, which may explain flight instabilities observed in freely flying bees.

Pachydermodactyly: A Case Report Including Histopathology.

Pachydermodactyly (PDD) is a rare form of digital fibromatosis characterized by painless soft tissue swelling, primarily about the proximal interphalangeal joints. The skin at the metacarpophalangeal joints, the palm, and the dorsum of the hand may also be involved. Because swelling can occur over the proximal interphalangeal and metacarpophalangeal joints, PDD may be confused with juvenile inflammatory arthropathy and may even occur concurrently. We present the clinical and histopathologic findings of a case of PDD characterized by bilateral proximal phalangeal involvement of the index through little fingers.

Shoulder and Elbow Recovery at 2 and 11 Years Following Brachial Plexus Reconstruction.

PURPOSE: To report short-term and long-term outcomes on a single patient cohort observed longitudinally after nerve reconstruction for adult brachial plexus injury. METHODS: Eleven male patients who underwent plexus reconstruction by the same surgeon at 2 institutions presented for clinical examination 7.5 or more years after surgery (average, 11.4 years; range, 7.5-22 years). Average age at the time of operation was 35 years (range, 17-73 years). Mean delay until surgery was 5 months (range, 2-11 months). Two patients had C5 paralysis, 2 had C5-C6 paralysis, 2 had C5-C7 paralysis, and 5 had complete 5-level injuries. Outcome parameters included active range of motion (ROM) in degrees, a modified British Medical Research Council (mBMRC) scale for muscle strength, and electromyographic motor unit configuration and recruitment pattern. Differences in ROM and mBMRC between 2-year and long-term follow-up were assessed with paired-sample t tests using an alpha value of .05. RESULTS: Average shoulder abduction and mBMRC at final follow-up were both significantly improved compared with the 2-year follow-up results (P < .05). Average elbow flexion and mBMRC increased significantly between 2 years and final follow-up (P < .05). Electromyographic results for 6 patients at final follow-up showed improved motor unit configuration in 10 of 15 muscles and improved recruitment in 3 of 15 muscles compared with 2-year electromyographic results. CONCLUSIONS: Patients continued to gain ROM and strength in the shoulder and elbow well after 2 to 3 years after surgery, contrary to previous reports. Although the precise mechanism is unknown, we speculate that a number of factors may be involved, including terminal collateral sprouting, maturation of motor units, improvements in motor unit recruitment, additional muscle fiber hypertrophy, or an as-yet undescribed mechanism. We recommend that patients be encouraged to continue strengthening exercises well after the initial recovery period and that more comparative long-term data be collected to expand on these observations.

Consumer exposure modelling under REACH: Assessing the defaults.

Consumer exposure to chemicals from products and articles is rarely monitored. Since an assessment of consumer exposure has become particularly important under the European REACH Regulation, dedicated modelling approaches with exposure assessment tools are applied. The results of these tools are critically dependent on the default input values embedded in the tools. These inputs were therefore compiled for three lower tier tools (ECETOC TRA (version 3.0), EGRET and REACT)) and benchmarked against a higher tier tool (ConsExpo (version 4.1)). Mostly, conservative input values are used in the lower tier tools. Some cases were identified where the lower tier tools used less conservative values than ConsExpo. However, these deviations only rarely resulted in less conservative exposure estimates compared to ConsExpo, when tested in reference scenarios. This finding is mainly due to the conservatism of (a) the default value for the thickness of the product layer (with complete release of the substance) used for the prediction of dermal exposure and (b) the complete release assumed for volatile substances (i.e. substances with a vapour pressure ⩾10Pa) for inhalation exposure estimates. The examples demonstrate that care must be taken when changing critical defaults in order to retain conservative estimates of consumer exposure to chemicals.

Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study.

The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.

Recurrent pigmented villonodular synovitis and multifocal giant cell tumor of the tendon sheath: case report.

Intra- and extra-articular giant cell tumor of tendon sheath (GCTTS) and pigmented villonodular synovitis (PVNS) are histologically similar, usually benign tumors that can be characterized by synovial involvement (GCTTS) or overgrowth (PVNS). These tumors are most often found in the knee and digits of the hand. Although recurrence is a common feature of both conditions, multifocal lesions are rare. We present an unusual case of multifocal, recurrent, bilateral GCTTS/PVNS involving both upper and lower extremities. Recurrent right ankle and right index finger masses, in addition to masses on the right small finger and left thumb, were excised over a 14-year period.