A metabolomics perspective on 2 years of high-intensity training in horses.

The plasma metabolomic profile of elite harness horses subjected to different training programmes was explored. All horses had the same training programme from 1.5 until 2 years of age and then high-intensity training was introduced, with horses divided into high and low training groups. Morning blood samples were collected at 1.5, 2, 2.5 and 3.5 years of age. The plasma was analysed using targeted absolute quantitative analysis and a combination of tandem mass spectrometry, flow-injection analysis and liquid chromatography. Differences between the two training groups were observed at 2 years of age, when 161 metabolites and sums and ratios were lower (e.g. ceramide and several triglycerides) and 51 were higher (e.g. aconitic acid, anserine, sum of PUFA cholesteryl esters and solely ketogenic AAs) in High compared with low horses. The metabolites aconitic acid, anserine, leucine, HArg synthesis and sum of solely ketogenic AAs increased over time, while beta alanine synthesis, ceramides and indole decreased. Therefore high-intensity training promoted adaptations linked to aerobic energy production and amino acid metabolism, and potentially also affected pH-buffering and vascular and insulin responses.

Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow-derived hematopoietic progenitor cells and change their osteoclast-modulating effect.

Low-intensity loading maintains or increases bone mass, whereas lack of mechanical loading and high-intensity loading decreases bone mass, possibly via the release of extracellular vesicles by mechanosensitive bone cells. How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7 ± 0.3 Pa, 5 Hz) or high intensity (2.9 ± 0.2 Pa, 1 Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa-Β ligand-induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10 000× g) obtained after low-intensity loading and induced by exosomes (100 000× g) obtained after high-intensity loading. These osteoclast-modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT-independent exosome biogenesis (high intensity), as well as by inhibition of dynamin-dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast-modulating effect.

Conversion efficiency of flight power is low, but increases with flight speed in the migratory bat Pipistrellus nathusii.

The efficiency with which flying animals convert metabolic power to mechanical power dictates an individual's flight behaviour and energy requirements. Despite the significance of this parameter, we lack empirical data on conversion efficiency for most species as in vivo measurements are notoriously difficult to obtain. Furthermore, conversion efficiency is often assumed to be constant across flight speeds, even though the components driving flight power are speed-dependent. We show, through direct measurements of metabolic and aerodynamic power, that conversion efficiency in the migratory bat (Pipistrellus nathusii) increases from 7.0 to 10.4% with flight speed. Our findings suggest that peak conversion efficiency in this species occurs near maximum range speed, where the cost of transport is minimized. A meta-analysis of 16 bird and 8 bat species revealed a positive scaling relationship between estimated conversion efficiency and body mass, with no discernible differences between bats and birds. This has profound consequences for modelling flight behaviour as estimates assuming 23% efficiency underestimate metabolic costs for P. nathusii by almost 50% on average (36-62%). Our findings suggest that conversion efficiency may vary around an ecologically relevant optimum speed and provide a crucial baseline for investigating whether this drives variation in conversion efficiency between species.

Improved fracture risk prediction by adding VFA-identified vertebral fracture data to BMD by DXA and clinical risk factors used in FRAX.

Vertebral fracture (VF) is a strong predictor of subsequent fracture. In this study of older women, VF, identified by dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA), were associated with an increased risk of incident fractures and had a substantial impact on fracture probability, supporting the utility of VFA in clinical practice. PURPOSE: Clinical and occult VF can be identified using VFA with dual-energy X-ray absorptiometry (DXA). The aim of this study was to investigate to what extent VFA-identified VF improve fracture risk prediction, independently of bone mineral density (BMD) and clinical risk factors used in FRAX. METHODS: A total of 2852 women, 75-80 years old, from the prospective population-based study SUPERB cohort, were included in this study. At baseline, BMD was measured by DXA, VF diagnosed by VFA, and questionnaires used to collect data on risk factors for fractures. Incident fractures were captured by X-ray records or by diagnosis codes. An extension of Poisson regression was used to estimate the association between VFA-identified VF and the risk of fracture and the 5- and 10-year probability of major osteoporotic fracture (MOF) was calculated from the hazard functions for fracture and death. RESULTS: During a median follow-up of 5.15 years (IQR 4.3-5.9 years), the number of women who died or suffered a MOF, clinical VF, or hip fracture was 229, 422, 160, and 124, respectively. A VFA-identified VF was associated with an increased risk of incident MOF (hazard ratio [HR] = 1.78; 95% confidence interval [CI] 1.46-2.18), clinical VF (HR = 2.88; 95% [CI] 2.11-3.93), and hip fracture (HR = 1.67; 95% [CI] 1.15-2.42), adjusted for age, height, and weight. For women at age 75 years, a VFA-identified VF was associated with 1.2-1.4-fold greater 10-year MOF probability compared with not taking VFA into account, depending on BMD. CONCLUSION: Identifying an occult VF using VFA has a substantial impact on fracture probability, indicating that VFA is an efficient method to improve fracture prediction in older women.

Complement activation prior to symptom onset in myeloperoxidase ANCA-associated vasculitis but not proteinase 3 ANCA associated vasculitis - A Swedish biobank study.

OBJECTIVE: Increased soluble levels of complement effectors have been demonstrated in active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but the timing of complement activation in the autoimmune inflammation remains elusive. This study investigated whether the complement system is activated before onset of symptoms in AAV. METHOD: The Swedish National Patient Register and Cause of Death register were linked to registers of five biobanks to identify individuals sampled before AAV symptom onset. Diagnosis of AAV and time-point for symptom onset were confirmed by reviewing medical records. We identified 64 presymptomatic individuals with serum samples > 1 month < 10 years from AAV symptom onset and 122 matched controls. Complement factors (C2, C5) and activation markers (C5a, C4b) were measured using Luminex technology. RESULTS: Presymptomatic individuals had higher levels of C5 up to 6.5 years before symptom onset, compared with controls [median (IQR) 80.7 (131.9) vs 46.6 (63.4) µg/mL, p = 0.05]. Levels of C5a increased significantly during the pre-dating time (p = 0.033) until symptom onset. The complement levels were significantly higher in presymptomatic myeloperoxidase (MPO)-ANCA+ individuals versus MPO-ANCA- and proteinase-3-ANCA+ individuals. C5 was significantly increased in cases with renal involvement at diagnosis versus controls (p = 0.022), whereas levels of both C5 and C5a were significantly increased in presymptomatic individuals diagnosed with microscopic polyangiitis after onset compared with controls (C5: p = 0.027; C5a: p = 0.027). CONCLUSION: Activation of the complement system is an early event in the pathogenesis of AAV and is mainly associated with MPO-ANCA+ AAV and with microscopic polyangiitis.

One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD.

In women of ages 75-80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. INTRODUCTION: Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. METHODS: The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75-80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. RESULTS: During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49-6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34-1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26-2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). CONCLUSION: A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women.

Downstroke and upstroke conflict during banked turns in butterflies.

For all flyers, aeroplanes or animals, making banked turns involve a rolling motion which, due to higher induced drag on the outer than the inner wing, results in a yawing torque opposite to the turn. This adverse yaw torque can be counteracted using a tail, but how animals that lack tail, e.g. all insects, handle this problem is not fully understood. Here, we quantify the performance of turning take-off flights in butterflies and find that they use force vectoring during banked turns without fully compensating for adverse yaw. This lowers their turning performance, increasing turn radius, since thrust becomes misaligned with the flight path. The separation of function between downstroke (lift production) and upstroke (thrust production) in our butterflies, in combination with a more pronounced adverse yaw during the upstroke increases the misalignment of the thrust. This may be a cost the butterflies pay for the efficient thrust-generating upstroke clap, but also other insects fail to rectify adverse yaw during escape manoeuvres, suggesting a general feature in functionally two-winged insect flight. When lacking tail and left with costly approaches to counteract adverse yaw, costs of flying with adverse yaw may be outweighed by the benefits of maintaining thrust and flight speed.

Hovering flight in hummingbird hawkmoths: kinematics, wake dynamics and aerodynamic power.

Hovering insects are divided into two categories: 'normal' hoverers that move the wing symmetrically in a horizontal stroke plane, and those with an inclined stroke plane. Normal hoverers have been suggested to support their weight during both downstroke and upstroke, shedding vortex rings each half-stroke. Insects with an inclined stroke plane should, according to theory, produce flight forces only during downstroke, and only generate one set of vortices. The type of hovering is thus linked to the power required to hover. Previous efforts to characterize the wake of hovering insects have used low-resolution experimental techniques or simulated the flow using computational fluid dynamics, and so it remains to be determined whether insect wakes can be represented by any of the suggested models. Here, we used tomographic particle image velocimetry, with a horizontal measurement volume placed below the animals, to show that the wake shed by hovering hawkmoths is best described as a series of bilateral, stacked vortex 'rings'. While the upstroke is aerodynamically active, despite an inclined stroke plane, it produces weaker vortices than the downstroke. In addition, compared with the near wake, the far wake lacks structure and is less concentrated. Both near and far wakes are clearly affected by vortex interactions, suggesting caution is required when interpreting wake topologies. We also estimated induced power (Pind) from downwash velocities in the wake. Standard models predicted a Pind more than double that from our wake measurements. Our results thus question some model assumptions and we propose a reevaluation of the model parameters.

Butterflies fly using efficient propulsive clap mechanism owing to flexible wings.

Butterflies look like no other flying animal, with unusually short, broad and large wings relative to their body size. Previous studies have suggested butterflies use several unsteady aerodynamic mechanisms to boost force production with upstroke wing clap being a prominent feature. When the wings clap together at the end of upstroke the air between the wings is pressed out, creating a jet, pushing the animal in the opposite direction. Although viewed, for the last 50 years, as a crucial mechanism in insect flight, quantitative aerodynamic measurements of the clap in freely flying animals are lacking. Using quantitative flow measurements behind freely flying butterflies during take-off and a mechanical clapper, we provide aerodynamic performance estimates for the wing clap. We show that flexible butterfly wings, forming a cupped shape during the upstroke and clap, thrust the butterfly forwards, while the downstroke is used for weight support. We further show that flexible wings dramatically increase the useful impulse (+22%) and efficiency (+28%) of the clap compared to rigid wings. Combined, our results suggest butterflies evolved a highly effective clap, which provides a mechanistic hypothesis for their unique wing morphology. Furthermore, our findings could aid the design of man-made flapping drones, boosting propulsive performance.

The timed up and go test predicts fracture risk in older women independently of clinical risk factors and bone mineral density.

The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. INTRODUCTION: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. METHODS: A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75-80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. RESULTS: Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80-3.18] and hip fracture 2.96 [1.62-5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5-1.9 in a 75-year-old woman with slow TUG (> 12 s). CONCLUSION: The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women.

Association between inflammasome-related polymorphisms and psoriatic arthritis.

Objective: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease associated with psoriasis. Underlying genetic factors are considered important for disease expression and prognosis of PsA. Interleukin-1ß-regulating protein complexes called inflammasomes are associated with several inflammatory diseases, e.g. rheumatoid arthritis and psoriasis. The aim was to determine whether inflammasome-related genetic variation is associated with PsA susceptibility or different disease phenotypes.Method: DNA from 724 patients with PsA and 587 population-based controls from northern Sweden was analysed for single-nucleotide polymorphisms in NLRP3-Q750K (rs35829419), NLRP3 (rs10733113), CARD8-C10X (rs2043211), NLRP1 (rs8079034), and NLRP1 (rs878329).Results: Significant associations were found with the genotype AA (vs AT+TT) of rs2043211 for PsA patients compared with controls [odds ratio (OR), 95% confidence interval (CI) 1.32 (1.05-1.65), p = 0.016]; and between the C-allele of rs878329 and axial involvement of PsA [OR (95% CI) 1.37 (1.02-1.84), p = 0.035], the T-allele of rs8079034 with prescription of conventional synthetic disease-modifying anti-rheumatic drugs [OR (95% CI) 1.76 (1.23-2.53), p = 0.0020], the G-allele of rs10733113 and patients with a skin disease with early onset [OR (95% CI) 1.58 (1.13-2.21), p = 0.007], and the C-allele of rs35829419 and a destructive/deforming disease [OR (95% CI) 1.63 (1.04-2.55), p = 0.030].Conclusions: This study is the first to show an association with a genetic polymorphism in an inflammasome-related gene, CARD8-C10X (rs2043211), in patients with PsA. Associations between different phenotypes of PsA and different polymorphisms of the inflammasome genes were also found. Our results indicate the involvement of inflammasome genes in the pathogenesis and disease expression of PsA.

On the early stages of localised atmospheric corrosion of magnesium-aluminium alloys.

The surface film on pure magnesium and two aluminium-containing magnesium alloys was characterised after 96 h at 95% RH and 22 °C. The concentration of CO2 was carefully controlled to be either 0 or 400 ppm. The exposed samples were investigated using X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and electron microscopy. The results showed that when the alloys were exposed to the CO2-containing environment, aluminium cations (Al3+) was incorporated into a layered surface film comprising a partially "hydrated" MgO layer followed by Mg(OH)2, and magnesium hydroxy carbonates. The results indicated that aluminium-containing magnesium alloys exhibited considerably less localised corrosion in humid air than pure magnesium. Localised corrosion in the materials under investigation was attributed to film thinning by a dissolution/precipitation mechanism.

Measuring power input, power output and energy conversion efficiency in un-instrumented flying birds.

Cost of flight at various speeds is a crucial determinant of flight behaviour in birds. Aerodynamic models, predicting that mechanical power (Pmech) varies with flight speed in a U-shaped manner, have been used together with an energy conversion factor (efficiency) to estimate metabolic power (Pmet). Despite few empirical studies, efficiency has been assumed constant across flight speeds at 23%. Ideally, efficiency should be estimated from measurements of both Pmech and Pmet in un-instrumented flight. Until recently, progress has been hampered by methodological constraints. The main aim of this study was to evaluate recently developed techniques and estimate flight efficiency across flight speeds. We used the 13C-labelled sodium bicarbonate method (NaBi) and particle image velocimetry (PIV) to measure Pmet and Pmech in blackcaps flying in a wind tunnel. We also cross-validated measurements made by NaBi with quantitative magnetic resonance (QMR) body composition analysis in yellow-rumped warblers. We found that Pmet estimated by NaBi was ∼12% lower than corresponding values estimated by QMR. Pmet varied in a U-shaped manner across flight speeds in blackcaps, but the pattern was not statistically significant. Pmech could only be reliably measured for two intermediate speeds and estimated efficiency ranged between 14% and 22% (combining the two speeds for raw and weight/lift-specific power, with and without correction for the ∼12% difference between NaBi and QMR), which were close to the currently used default value. We conclude that NaBi and PIV are viable techniques, allowing researchers to address some of the outstanding questions regarding bird flight energetics.

Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.

BACKGROUND: Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. METHODS: An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. RESULTS: Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. CONCLUSION: Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.

ANTECEDENTES: La cirugía de la aganglionosis colónica total (total colonic aganglionosis, TCA) está diseñada para preservar la continencia y lograr una calidad de vida satisfactoria. Este estudio evaluó un gran número de resultados clínicos y sociales. MÉTODOS: Se realizó un estudio internacional multicéntrico en ocho hospitales nórdicos en el que se incluyeron las historias clínicas de todos los pacientes nacidos con TCA entre 1987 y 2006. Se invitó a los pacientes y a sus cuidadores a responder una encuesta sobre la función intestinal, el crecimiento y las necesidades nutricionales, así como la repercusión social de la enfermedad a largo plazo. RESULTADOS: De un total de 116 pacientes, 5 (4,3%) habían fallecido y 102 respondieron la encuesta. Con una mediana de seguimiento de 12 años (rango 0,5-33), se había restablecido la continuidad intestinal en 75/102 (74%) a una mediana de edad de 11 meses (0,5-156). La mucosectomía con un manguito muscular corto y anastomosis ileoanal directa (short muscular cuff and straight ileo-anal anastomosis, SIAA) n = 29 o con reservorio en J (JIAA) n = 26 (55/72, 76%) fueron las reconstrucciones más habituales. Las complicaciones postoperatorias precoces que precisaron una intervención quirúrgica fueron muy poco frecuentes, pero se presentaron en 4/72 (5%) pacientes. Los síntomas a largo plazo relacionados con la función intestinal tras la reconstrucción, valorados en 57 niños mayores de cuatro años, fueron la dificultad para retener la defecación en 14 (25%), la encopresis en 21 (37%), las pérdidas fecales > 1/semana en 9 (16%) y el aumento de la frecuencia de defecación en 51 (89%). A largo plazo, se desarrolló una enterocolitis en 35/72 (47%) pacientes. Se precisó de nutrición enteral y/o parenteral suplementaria en algún momento del período de seguimiento en 51/93 (55%) pacientes. En los pacientes que respondieron a la encuesta entre 2 y 20 años (n = 56) de edad, se detectó un índice de masa corporal menor en 20 (35%) y una altura baja en 13 (23%) para su edad. En 35/57 (61%) pacientes mayores de 4 años con restauración del tránsito intestinal había restricciones sociales debido a los síntomas intestinales, de los que en 10 (17%) casos fueron moderadas o graves. CONCLUSIÓN: La reconstrucción de una TCA se asocia con síntomas intestinales persistentes y la enterocolitis sigue siendo frecuente. Un seguimiento multidisciplinario, incluso en la edad adulta, podría mejorar los resultados en la cirugía de la TCA.

Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death.

Because of its key role in cancer development and progression, STAT3 has become an attractive target for developing new cancer therapeutics. While several STAT3 inhibitors have progressed to advanced stages of development, their underlying biology and mechanisms of action are often more complex than would be expected from specific binding to STAT3. Here, we have identified and optimized a series of compounds that block STAT3-dependent luciferase expression with nanomolar potency. Unexpectedly, our lead compounds did not bind to cellular STAT3 but to another prominent anticancer drug target, TrxR1. We further identified that TrxR1 inhibition induced Prx2 and STAT3 oxidation, which subsequently blocked STAT3-dependent transcription. Moreover, previously identified inhibitors of STAT3 were also found to inhibit TrxR1, and likewise, established TrxR1 inhibitors block STAT3-dependent transcriptional activity. These results provide new insights into the complexities of STAT3 redox regulation while highlighting a novel mechanism to block aberrant STAT3 signaling in cancer cells.

Decreased physical health-related quality of life-a persisting state for older women with clinical vertebral fracture.

In a population-based study of older Swedish women, we investigated if clinical vertebral fracture was associated with lower health-related quality of life (HRQoL) and determined whether the association remained over time. Clinical vertebral fracture was associated with lower HRQoL and the effect persisted for up to 18.9 years. INTRODUCTION: Vertebral fractures are often associated with back pain and reduced physical function, which might result in isolation and depression. As a result, women with vertebral fractures often have lower health-related quality of life (HRQoL), but during what time frame the decrease lingers is unclear. Therefore, the aim of this study was to investigate if clinical vertebral fracture and hip fracture were associated with lower HRQoL and to determine whether the associations remained over time. METHODS: Vertebral fracture assessments (VFA) were performed using dual-energy X-ray absorptiometry. Data regarding prior fractures, medications, medical history, and physical activity was collected using a questionnaire. Self-rated physical HRQoL was assessed using the 12-Item Short-Form Health Survey (SF-12). Women with clinical vertebral fractures were divided into tertiles according to time since fracture onset and their HRQoL was compared with non-fractured women. RESULTS: In a population-based cross-sectional study of 3028 women aged 77.8 ± 1.63 (mean ± SD), a total of 130 (4.3%) women reported at least one clinical vertebral fracture. Women with a clinical vertebral fracture, divided into tertiles (T1-T3) depending on time since the fracture occurred, had lower HRQoL (T1: 36.3 ± 10.8; T2: 41.0 ± 9.94; and T3:41.6 ± 11.4) than women without fracture (46.2 ± 10.6; p < 0.001). Using linear regression analysis, clinical vertebral fracture was associated with reduced physical HRQoL for up to 18.9 years, independently of covariates (age, height, weight, smoking, prior stroke, mental HRQoL, grip strength, and lumbar spine BMD). CONCLUSIONS: Clinical vertebral fracture was associated with lower self-rated physical HRQoL, for up to 18.9 years after time of fracture.

Preoperative aortic annulus size assessment by transthoracic echocardiography compared to the size of surgically implanted aortic prostheses.

OBJECTIVES: The aortic annulus diameter measured by transthoracic echocardiography yields lower values than by computed tomography, and echo-based selection of transcatheter aortic valve prosthesis size has been implied to result in more frequent paravalvular leakage. We investigated the relation of preoperative annulus diameter by echo with the ring size of the aortic prosthesis chosen by direct assessment during open-heart aortic valve replacement. METHODS: Preoperative annulus diameter by echo (from parasternal long-axis cross-sections of the left ventricular outflow tract and aortic valve) and implanted prosthetic diameter (tissue annulus diameter, determined intraoperatively using a sizing instrument) were compared retrospectively in 285 consecutive patients undergoing open-heart aortic valve replacement. RESULTS: A total of 285 prostheses (240 biologic and 45 mechanical) were implanted, with prosthetic diameter ranging between 19 and 27 mm. There was a significant linear correlation (P < 0.0001) with r = 0.51, between preoperative annulus diameter by echo (mean 21.8 ± 2.8 mm) and prosthetic diameter (22.9 ± 1.7 mm). Preoperative annulus diameter of patients receiving prostheses no. 21, 23 and 25 mm aortic prostheses (the most frequent prosthesis sizes) were significantly different (P < 0.001) from each other. On average, preoperative annulus diameter by echo underestimated prosthetic diameter by a bias of 1.07 mm. CONCLUSION: Our data confirm that preoperative echo assessment of the aortic valve may slightly underestimates the optimal surgical prosthesis diameter for the aortic valve annulus.

Scanning tunneling microscopy study of PTCDI on Sn/Si(111)-23×23.

Perylene tetracarboxylic diimide molecules were evaporated onto a Sn/Si(111)-23×23 surface and studied using scanning tunneling microscopy (STM) and low energy electron diffraction. At low coverages, single molecules are locked into specific adsorption geometries, which are investigated in detail using high resolution STM. The electronic structure of these individual molecules was studied using bias dependent STM images. The molecules form 1D rows that become more common with increasing coverages. Possible intermolecular O⋯H interactions within the rows have been identified. At around half of a monolayer (ML), the rows of molecules interact with each other and form a commensurate 43×23 reconstruction. In a complete monolayer, several structures emerge as molecules fill in the space between the 43×23 stripes. Possible intermolecular interactions within the 1 ML structures have been discussed. At coverages above 1 ML, the growth is characterized by island growth, where the molecules are arranged according to the canted structure within the layers.

Delicate interactions of PTCDI molecules on Ag/Si(111)- 3 × 3 .

PTCDI molecules were evaporated onto a Ag/Si(111) 3 × 3 surface and studied using scanning tunneling microscopy (STM) and angular resolved ultraviolet photoelectron spectroscopy (ARUPS). High resolution STM images are used to identify the delicate molecule/molecule and molecule/substrate interactions and the shapes of the molecular orbitals. The results show that the substrate/molecule interaction strongly modifies the electronic configuration of the molecules as their orbital shapes are quite different at 1 and 2 monolayer (ML) coverage. Simple models of molecular HOMO/LUMO levels and intermolecular hydrogen-bondings have been made for 1 and 2 ML PTCDI coverages to explain the STM images. Changes due to the interaction with the substrate are also found in ARUPS as extra states above the regular HOMO level at 1 ML PTCDI coverage. The ARUPS data also show that the electronic structure of the substrate remains unchanged after the deposition of molecules as the dispersion of the substrate related bands is unchanged. The changes in electronic structure of the molecules are discussed based on a HOMO/LUMO split.

Flight in Ground Effect Dramatically Reduces Aerodynamic Costs in Bats.

Most flying animals, from insects to seabirds [1], perform flights close to ground or water when taking off or landing [2], drinking, and feeding [3-5] or when traveling near water surfaces [1, 6, 7]. When flying close to a surface within approximately one wingspan, the surface acts as an aerodynamic mirror, interrupting the downwash [8, 9], resulting in increased pressure underneath the wing and suppression of wingtip vortex development [10]. This aerodynamic interaction lowers the energy added to the air by the animal, reducing the cost of flying. Modeling suggests that flapping wings in ground effect can affect the expected power savings compared to gliding flight, either positively or negatively, depending on the wing motion [11-13]. Although aerodynamic theory predicts substantial power reductions when animals fly in ground effect [4-6, 9, 11, 12], quantitative measurements of savings are lacking. Here, we show, through wake-based power measurements, that Daubenton's bats utilize 29% less aerodynamic power when flying in compared to out of ground effect, which is twice the predicted savings. Contrary to theoretical predictions [4-6, 9, 11, 12] we find no variation in savings with distance above ground when in ground effect. Given alterations in kinematics with ground proximity, we hypothesize that modulation of wing kinematics raises the achievable benefit from ground effect relative to current model predictions. The savings from ground effect are comparable to formation flight [14, 15] but are not limited to large bird species. Instead, ground effect is experienced by most flying animals and may have facilitated the evolution of powered animal flight.