Changes in social isolation and loneliness following total hip and knee arthroplasty: longitudinal analysis of the English Longitudinal Study of Ageing (ELSA) cohort.

OBJECTIVE: To determine the prevalence and change in social isolation and loneliness in people before and after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in England. DESIGN: The English Longitudinal Study of Ageing (ELSA) dataset, a prospective study of community-dwelling older adults, was used to identify people who had undergone primary THA or TKA because of osteoarthritis. Social isolation was assessed using the ELSA Social Isolation Index. Loneliness was evaluated using the Revised University of California, Los Angeles (UCLA) Loneliness Scale. The prevalence of social isolation and loneliness were calculated and multilevel modelling was performed to assess the potential change of these measures before arthroplasty, within a two-year operative-recovery phase and a following two-year follow-up. RESULTS: The sample consisted of 393 people following THA and TKA. The prevalence of social isolation and loneliness changed from 16.9% to 18.8% pre-operative to 21.8% and 18.9% at the final post-operative follow-up respectively. This was not a statistically significant change for either measure (P = 0.15; P = 0.74). There was a significant difference in social isolation at the recovery phase compared to the pre-operative phase (P = 0.01), where people following arthroplasty reported an increase in social isolation (16.9-21.4%). There was no significant difference between the assessment phases in respect to UCLA Loneliness Scale score (P ≥ 0.74). CONCLUSIONS: Given the negative physical and psychological consequences which social isolation and loneliness can have on individuals following THA or TKA, clinicians should be mindful of this health challenge for this population. The reported prevalence of social isolation and loneliness suggests this is an important issue.

Zinc absorption in Brazilian subjects fed a healthy meal.

BACKGROUND: The high amounts of phytic acid present in diets from developing countries are considered as important inhibitors of zinc (Zn) absorption. The present study aimed to assess the fractional absorption of Zn from a meal containing common Brazilian foods using the stable isotope technique. METHODS: Twelve men, aged 19-42 years, were fed a healthy experimental diet comprising lettuce, tomato, French fries, steak with onions, rice, beans, papaya, orange, pineapple, and passion fruit juice. Each subject received one intravenous dose of enriched (70) Zn, and the lunch was extrinsically labelled with enriched (67) Zn. Urinary (67) Zn and (70) Zn enrichments were assessed by inductively coupled plasma mass spectrometry. RESULTS: The labelled meal phytate : Zn molar ratio was very divergent with respect to chemically determined and calculated data. Subjects presented a normal Zn nutritional status before and after the study. The mean Zn absorption from the labelled meal was 30% (range 11-47%). CONCLUSIONS: According to the World Health Organization parameters, the results denote a moderate/high Zn bioavailability in the evaluated meal, with a variability in the absorption percentage that is similar to other studies. The data show that a typical Brazilian meal, with an adequate energy amount and a balanced macronutrient distribution, presents a Zn bioavailability in accordance with the worldwide recommended standard.

Fast vectorial calculation of the volumetric focused field distribution by using a three-dimensional Fourier transform.

We show that the volumetric field distribution in the focal region of a high numerical aperture focusing system can be efficiently calculated with a three-dimensional Fourier transform. In addition to focusing in a single medium, the method is able to calculate the more complex case of focusing through a planar interface between two media of mismatched refractive indices. The use of the chirp z-transform in our numerical implementation of the method allows us to perform fast calculations of the three-dimensional focused field distribution with good accuracy.

Ambiguity of optical coherence tomography measurements due to rough surface scattering.

Optical coherence tomography (OCT) images are frequently interpreted in terms of layers (for example, of tissue) with the boundary defined by a change in refractive index. Real boundaries are rough compared with the wavelength of light, and in this paper we show that this roughness has to be taken into account in interpreting the images. We give an example of the same OCT image obtained from two quite different objects, one smooth compared to the optical wavelength, and the other rough.

Direct calculation of a three-dimensional diffracted field.

We present an approach to calculating the complex amplitude of a three-dimensional (3D) diffracted light field in the paraxial approximation based on a 3D Fourier transform. Starting from the Huygens-Fresnel principle, the method is first developed for the computation of the light distribution around the focus of an apertured spherical wave. The method, with modification, is then extended to treat the 3D diffraction of an aperture with an arbitrary transmittance function.

Pupil matching of Zernike aberrations.

The measurement of the wavefront at the exit pupil of an optical system is a reliable method to investigate its imaging performance. It is sometimes necessary to compare the measurement obtained with a wavefront sensor to some known aberration function, which is for example given by a simulation or a gold standard measurement technique such as interferometry. For accurate measurement systems, the residual after direct subtraction of the two wavefronts is often partly due to a mismatch between coordinate systems. We present in this paper a method that uses the Zernike expansion of wavefronts to numerically cancel such small alignment errors. We use this algorithm to quantify the accuracy of a custom-built Shack-Hartmann wavefront sensor in the measurement of known aberration functions.

Application of orbital angular momentum to simultaneous determination of tilt and lateral displacement of a misaligned laser beam.

We present an analysis of the combined effects of tilt and lateral displacement on the orbital angular momentum spectrum of a laser beam. Our theory explains the symmetries and properties of the spectrum under the influence of misalignments. We apply the theory to establish a reliable and efficient method for determining and subsequently eliminating tilt and lateral displacement. An improved technique for obtaining the orbital angular momentum spectrum employing Laguerre-Gaussian modes is proposed. Finally, a numerical experiment is carried out to verify the method.

Profiling CpG island field methylation in both morphologically normal and neoplastic human colonic mucosa.

Aberrant CpG island (CGI) methylation occurs early in colorectal neoplasia. Quantitative methylation-specific PCR profiling applied to biopsies was used to quantify low levels of CGI methylation of 18 genes in the morphologically normal colonic mucosa of neoplasia-free subjects, adenomatous polyp patients, cancer patients and their tumours. Multivariate statistical analyses distinguished tumour from mucosa with a sensitivity of 78.9% and a specificity of 100% (P=3 x 10(-7)). In morphologically normal mucosa, age-dependent CGI methylation was observed for APC, AXIN2, DKK1, HPP1, N33, p16, SFRP1, SFRP2 and SFRP4 genes, and significant differences in CGI methylation levels were detected between groups. Multinomial logistic regression models based on the CGI methylation profiles from normal mucosa correctly identified 78.9% of cancer patients and 87.9% of non-cancer (neoplasia-free+polyp) patients (P=4.93 x 10(-7)) using APC, HPP1, p16, SFRP4, WIF1 and ESR1 methylation as the most informative variables. Similarly, CGI methylation of SFRP4, SFRP5 and WIF1 correctly identified 61.5% of polyp patients and 78.9% of neoplasia-free subjects (P=0.0167). The apparently normal mucosal field of patients presenting with neoplasia has evidently undergone significant epigenetic modification. Methylation of the genes selected by the models may play a role in the earliest stages of the development of colorectal neoplasia.

Does physical activity change following hip and knee replacement? Matched case-control study evaluating Physical Activity Scale for the Elderly data from the Osteoarthritis Initiative.

OBJECTIVES: To determine whether physical activity measured using the Physical Activity Scale for the Elderly (PASE), changes during the initial 24 months post-total hip (THR) or knee replacement (TKR), and how this compares to a matched non-arthroplasty cohort. DESIGN: Case-controlled study analysis of a prospectively collected dataset. SETTING: USA community-based. PARTICIPANTS: 116 people post-THR, 105 people post-TKR compared to 663 people who had not undergone THR or TKR, or had hip or knee osteoarthritis. Cohorts were age-, gender- and BMI-matched. MAIN OUTCOME MEASURES: Physical activity assessed using the 12-item PASE at 12 and 24 months post operatively. RESULTS: There was no significant difference in total PASE score between pre-operative to 12 months (mean: 136 vs 135 points; p=0.860) or 24 months following THR (mean: 136 vs 132 points; p=0.950). Whilst there was no significant difference in total PASE score from pre-operative to 12 months post-TKR (126 vs 121 points; p=0.930), by 24 months people following TKR reported significantly greater physical activity (126 vs 142 points; p=0.040). There was no statistically significant difference in physical activity between the normative matched and THR (p≥0.140) or TKR (p≥0.060) cohorts at 12 or 24 months post joint replacement. CONCLUSIONS: Physical activity is not appreciably different to pre-operative levels at 12 or 24 months post-THR, but was greater at 24 months following TKR. Health promotion strategies are needed to encourage greater physical activity participation following joint replacement, and particularly targeting those who undergo THR.

Laboratory MCAO Test-Bed for Developing Wavefront Sensing Concepts.

An experimental optical bench test-bed for developing new wavefront sensing concepts for Multi-Conjugate Adaptive Optics (MCAO) systems is described. The main objective is to resolve imaging problems associated with wavefront sensing of the atmospheric turbulence for future MCAO systems on Extremely Large Telescopes (ELTs). The test-bed incorporates five reference sources, two deformable mirrors (DMs) and atmospheric phase screens to simulate a scaled version of a 10-m adaptive telescope operating at the K band. A recently proposed compact tomographic wavefront sensor is employed for star-oriented DMs control in the MCAO system. The MCAO test-bed is used to verify the feasibility of the wavefront sensing concept utilizing a field lenslet array for multi-pupil imaging on a single detector. First experimental results of MCAO correction with the proposed tomographic wavefront sensor are presented and compared to the theoretical prediction based on the characteristics of the phase screens, actuator density of the DMs and the guide star configuration.

Estimation of iron absorption in humans using compartmental modelling.

OBJECTIVE: To evaluate whether a compartmental model could estimate iron absorption as accurately as the well-validated technique of plasma area under the curve using labelled test meals. DESIGN: The study is a randomised cross-sectional intervention. SETTING: The study was carried out at the Human Nutrition Unit at the Institute of Food Research, Norwich, UK. SUBJECTS: A total of nine female volunteers, aged 33+/-8 y. INTERVENTIONS: Volunteers were given an oral dose (approximately 5 mg) of Fe-57 as iron sulphate in an orange juice test drink and simultaneously infused Fe-58 (approximately 200 microg) as iron citrate over 90 min. Multiple blood samples were taken for the following 6 h. The samples were analysed by mass spectrometry and iron absorption was estimated using a mathematical model based on the appearance of Fe isotopes in plasma and the area under the curve technique. RESULTS: The geometric mean (-1 s.d., +1 s.d.) absorption of the model estimate is 16% (9, 31) and the area under curve estimate is 18% (8, 29). CONCLUSIONS: Results indicate that a compartmental model can be used to estimate labelled iron absorption although it is unlikely that this new method will be used in favour of an existing one. Further studies are now needed with unlabelled iron to assess whether the technique could have application in the assessment of total (haem+nonhaem) iron absorption from food.

Copper absorption from foods labelled intrinsically and extrinsically with Cu-65 stable isotope.

OBJECTIVE: To determine copper absorption from copper containing foods labelled either intrinsically or extrinsically with a highly enriched Cu-65 stable isotope label. DESIGN: A longitudinal cross-over study. SETTING: The study was conducted at the Institute of Food Research, Human Nutrition Unit, Norwich, UK. SUBJECTS: Subjects were recruited locally via advertisements placed around the Norwich Research Park. A total of 10 volunteers (nine female, one male) took part in the study, but not all volunteers completed each of the test meals. INTERVENTIONS: A highly enriched Cu-65 stable isotope label was administered to volunteers in the form of a reference dose or in breakfast test meals consisting of red wine, soya beans, mushrooms or sunflower seeds. Faecal monitoring and mass spectrometry techniques were used to estimate the relative quantities of copper absorbed from the different test meals. RESULTS: True copper absorption from the reference dose (54%) was similar to extrinsically labelled red wine (49%) and intrinsically labelled sunflower seeds (52%), but significantly higher than extrinsically labelled mushrooms (35%), intrinsically (29%) and extrinsically (15%) labelled soya beans and extrinsically labelled sunflower seed (32%) test meals. CONCLUSIONS: The use of Cu-65 extrinsic labels in copper absorption studies requires validation according to the food being examined; intrinsic and extrinsic labelling produced significantly different results for sunflower seeds.

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults.

OBJECTIVES: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups. DESIGN: A randomized, double-blind intervention study. SUBJECTS: A total of 12 young (<30 y) and 12 middle-aged (> or =50 y) healthy volunteers were recruited. METHODS: Volunteers were randomized to receive daily supplementation with 400 mug folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [(2)H(2)]folic acid test doses using isotope kinetics in plasma. RESULTS: Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P = 0.03) and after (P = 0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P = 0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young (+50%; P = 0.05) but not in the middle-aged (+18%; P = 0.5) adults. CONCLUSIONS: Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults. SPONSORSHIP: Financial support was received from the European Union 5th Framework Programme (Grant QLRT-1999-00576).

A low cost adaptive optics system using a membrane mirror.

A low cost adaptive optics system constructed almost entirely of commercially available components is presented. The system uses a 37 actuator membrane mirror and operates at frame rates up to 800Hz using a single processor. Numerical modelling of the membrane mirror is used to optimize parameters of the system. The dynamic performance of the system is investigated in detail using a diffractive wavefront generator based on a ferroelectric spatial light modulator. This is used to produce wavefronts with time-varying aberrations. The ability of the system to correct for Kolmogorov turbulence with different strengths and effective wind speeds is measured experimentally using the wavefront generator.

High bioavailability of calcium in fortified Horlicks.

OBJECTIVE: To compare the bioavailability of calcium carbonate-fortified Horlicks with calcium naturally present in milk. DESIGN: Randomised crossover within-subject comparison using a double label stable isotope technique. SETTING: Institute of Food Research, Human Nutrition Unit. PARTICIPANTS: Sixteen pre-menopausal women aged 23-40 y, habituated to a high-calcium diet (mean 1240 mg/day). RESULTS: Mean true fractional calcium absorption was 38.8% (s.d.+/-14.5) from Horlicks and 21.2% (s.d.+/-4.6) from milk. Significantly more calcium was absorbed from a serving of Horlicks than from the same quantity of calcium present in 420 g semi-skimmed milk (P<0.001). CONCLUSIONS: Fortified Horlicks is a highly bioavailable source of calcium. A single serving, containing at least 500 mg calcium, provides half the reference nutrient intake for the population sub-group with the highest requirement (adolescent boys) and more than half for all others. SPONSORSHIP: SmithKline Beecham funded this research project.

Bioavailability of selenium from fish, yeast and selenate: a comparative study in humans using stable isotopes.

OBJECTIVE: To measure the bioavailability of selenium from cooked and raw fish in humans by estimating and comparing apparent absorption and retention of selenium in biosynthetically labelled fish with labelled selenate and biosynthetically labelled selenium in brewers yeast. DESIGN: The intervention study was a parallel, randomised, reference substance controlled design carried out at two different centres in Europe. SETTING: The human study was carried out at the Institute of Food Research, Norwich, UK and at TNO Nutrition and Food Research, Zeist, The Netherlands. SUBJECTS: In all, 35 male volunteers aged 18-50 y were recruited; 17 subjects were studied in Norwich (UK) and 18 in Zeist (Netherlands). All of the recruited subjects completed the study. INTERVENTIONS: Biosynthetically labelled trout fish (processed by two different methods), biosynthetically labelled brewers yeast and isotopically labelled selenate were used to estimate selenium apparent absorption and retention by quantitative analysis of stable isotope labels recovered in faeces and urine. Subjects consumed the labelled foods in four meals over two consecutive days and absorption was measured by the luminal disappearance method over 10 days. Urinary clearance of isotopic labels was measured over 7 days to enable retention to be calculated. RESULTS: Apparent absorption of selenium from fish was similar to selenate and there was no difference between the two processing methods used. However, retention of fish selenium was significantly higher than selenate (P<0.001). Apparent absorption and retention of yeast selenium was significantly different (P<0.001) from both fish selenium and selenate. CONCLUSION: Fish selenium is a highly bioavailable source of dietary selenium. Cooking did not affect selenium apparent absorption or retention from fish. Selenium from yeast is less bioavailable.

Optical and digital image processing in high-resolution electron microscopy.

A comparison is made of the deblurring by digital and optical processing of a single conventional bright field electron image of ferritin particles distributed on a carbon supporting film. The deblurring functions include the effects of the partial temporal and partial spatial coherence of the electron beam, the phase contrast transfer function of the objective lens and Weiner signal to noise optimisation. Practical aspects of the similar results achieved by the two methods are discussed. The relative advantages and disadvantages of the batch and interactive computer modes for picture processing are considered in an Appendix.

Use of stable isotopes and mathematical modelling to investigate human mineral metabolism.

Individuals have varying needs for minerals that are dependent, amongst other things, on their lifestyle, age and genetic makeup. Knowledge of exact individual nutritional requirements should lead to better health, increased quality of life and reduced need for expensive medical care. Bioavailability, nutrient-gene interactions and whole-body metabolism all need to be investigated further if we are to progress towards the goal of defining optimal health and nutritional status. The discussion which follows will critically review the latest developments in the area of metabolism for several of the minerals that are essential for human health: Ca, Zn, Cu and Se. Stable-isotope tracers and mathematical modelling are some of the tools being used to facilitate the greater understanding in uptake, utilisation and excretion of these minerals. Stable isotopes, administered in physiological doses, present little or no risk to volunteers and allow metabolic studies to be carried out in vulnerable population groups such as children and pregnant women. Intrinsic labelling of foodstuffs ensures that the tracer and the native mineral will behave similarly once inside the body. Advances in computing power and software dedicated to solving nutritional problems have made it possible for investigators to use mathematical modelling in their experimental work. Mineral metabolism is ideally suited to a form of modelling known as compartmental analysis, which allows rates of mineral transferand sizes of mineral stores to be calculated accurately without the need for invasive sampling of body tissues.

Iron absorption from a breakfast cereal: effects of EDTA compounds and ascorbic acid.

Sodium iron ethylenediaminetetracetic acid (NaFeEDTA) has been recommended for food fortification programmes to improve iron status but its performance in commercial products has not been evaluated. The effect of EDTA on iron absorption from fortified cornflakes, given as part of a typical Western breakfast, was determined in a double-blind randomised study with 20 non-anaemic female volunteers, using experimentally prepared iron compounds, enriched with 58Fe, and faecal monitoring. Five meals were compared: hydrogen reduced iron, hydrogen reduced iron plus Na2EDTA (molar ratio EDTA:Fe 1:2), hydrogen reduced iron plus NaFe(III)EDTA at two different molar ratios (EDTA:total Fe 1:3 and 1:2), and hydrogen reduced iron plus 15 mg ascorbic acid (ascorbic acid:Fe 1.3:1). The iron and EDTA compounds were accurately weighed into gelatine capsules and taken with unfortified cornflakes, semi-skimmed milk and tea on two consecutive days; the iron dose per meal was 3.75 mg. Iron absorption from all five test meals was measured in each volunteer with a minimum wash-out period of 2 weeks between tests. Geometric mean iron absorption (%) from the 5 tests was 14.1, 17.6, 20.6, 24.4 and 17.5 respectively (equivalent to 0.5-0.9 mg absorbed iron). There was a significantly higher iron absorption from the mixture of reduced iron and NaFe(III)EDTA (EDTA:Fe 1:2) than from reduced iron alone (p = 0.014). It is not known whether the higher absorption was from reduced iron or NaFeEDTA or both. Absorption was not increased significantly with NaFe(III)EDTA (EDTA:Fe 1:3), Na2EDTA (EDTA:Fe 1:2) or ascorbic acid (15 mg).

High precision isotope measurements reveal poor control of copper metabolism in parkinsonism.

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable (65)Cu isotope tracer. The analyses of blood serum (65)Cu/(63)Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.