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Background: Skin measurements of transepidermal water loss (TEWL) and stratum corneum hydration (SCH) reflect different aspects of skin physiology. Since epidermal water loss depends on epidermal‐to‐air water vapor gradients, a possible quantitative relationship between TEWL and SCH may exist. This investigation's purpose was to test the possible TEWL‐SCH relationship. Materials and Methods: SCH and TEWL were measured noninvasively on forearm and palmer thenar eminence (hand) in 40 young adults (20 males) along with total body fat percentage (FAT) via bioimpedance. Results: A significant positive nonlinear correlation (p < 0.001) was detected between SCH and TEWL in hands of the male cohort that occurred when SCH exceeded a threshold level. This threshold level was not exceeded in male or female forearms and forearms did not display a SCH‐TEWL correlation. There was a weak inverse dependence of TEWL on FAT on both forearm and hand (p < 0.05), but no SCH‐FAT relationship was observed. TEWL values on the forearm and hand were moderately correlated with each other (p = 0.002) but SCH values were not. Conclusion: The findings clarify the relationship between forearm and palmer hydration and TEWL values, and their relationship to total body fat percentages in young healthy adults. The significant correlation between palmer stratum corneum hydration and palmer TEWL that was discovered in the male but not the female cohort suggests a threshold hydration level for which TEWL depends both on skin barrier function and stratum corneum hydration. This implies that conditions with increased SCH may in part account for elevated TEWL values. [ABSTRACT FROM AUTHOR]

Blood pressure and bone metabolism appear to share commonalities in their physiologic regulation. Specific antihypertensive drug classes may also influence bone mineral density. However, current evidence from existing observational studies and randomised trials is insufficient to establish causal associations for blood pressure and use of blood pressure–lowering drugs with bone health outcomes, particularly with the risks of osteoporosis and fractures. The availability and access to relevant large-scale biomedical data sources as well as developments in study designs and analytical approaches provide opportunities to examine the nature of the association between blood pressure and bone health more reliably and in greater detail than has ever been possible. It is unlikely that a single source of data or study design can provide a definitive answer. However, with appropriate considerations of the strengths and limitations of the different data sources and analytical techniques, we should be able to advance our understanding of the role of raised blood pressure and its drug treatment on the risks of low bone mineral density and fractures. As elevated blood pressure is highly prevalent and blood pressure–lowering drugs are widely prescribed, even small effects of these exposures on bone health outcomes could be important at a population level. [ABSTRACT FROM AUTHOR]

The introduction of the FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well-validated risk factors for fracture with or without the use of bone mineral density. Since age-specific rates of fracture and death differ across the world, FRAX models are calibrated with regard to the epidemiology of hip fracture (preferably from national sources) and mortality (usually United Nations sources). Models are currently available for 73 nations or territories covering more than 80% of the world population. FRAX has been incorporated into more than 80 guidelines worldwide, although the nature of this application has been heterogeneous. The limitations of FRAX have been extensively reviewed. Arithmetic procedures have been proposed in order to address some of these limitations, which can be applied to conventional FRAX estimates to accommodate knowledge of dose exposure to glucocorticoids, concurrent data on lumbar spine bone mineral density, information on trabecular bone score, hip axis length, falls history, type 2 diabetes, immigration status and recency of prior fracture. [ABSTRACT FROM AUTHOR]

Summary: In a simulated population of older women, we demonstrate that an upward shift in the population distribution of BMD by approximately 0.3SD may decrease the risk of incident fractures to the same extent as an intervention targeted to those with T-score less than −2.5. Introduction: To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. Methods: We used a simulated cohort of 49,242 women with age and body mass index distribution from the UK, and prevalence of other clinical risk factors based on European FRAX® cohorts. Using FRAX probabilities of major osteoporotic fracture (MOF: hip, clinical vertebral, distal forearm, proximal humerus) and hip fracture, calculated with femoral neck BMD, we determined the expected number of fractures over 10 years, stratified by 10-year age band from 50 years. We then investigated the effect of (i) uplifting all individuals with T-score below −2.5 to be exactly −2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). Results: Overall, the high-risk strategy prevented 573 MOF including 465 hip fractures. Moving the BMD T-score distribution upward by 0.27SD gave an equivalent reduction in numbers of MOF; for hip fractures prevented, this was 0.35SD. A global upward 0.25SD BMD shift prevented 524 MOF including 354 hip fractures, with corresponding figures for an increase of 0.5SD being 973 MOF prevented and 640 hip fractures prevented. The ratio of hip fracture to MOF prevented differed by the two approaches, such that for the high-risk strategy, the ratio was 0.81, and for the population strategy was 0.68 (0.25SD BMD uplift) and 0.66 (0.5SD BMD uplift). The numbers of fractures prevented by the high-risk strategy increased with age. In contrast, the age-related increase in numbers of fractures prevented with the population strategy rose with age, but peaked in the 70–79-year age band and declined thereafter. Conclusions: Both strategies reduced the numbers of expected incident fractures, with contrasting relative impacts by age and fracture site. Whilst the current analysis used UK/European anthropometric/risk factor distributions, further analyses calibrated to the distributions in other settings globally may be readily undertaken. Overall, these findings support the investigation of both population level interventions and those targeted at high fracture risk groups. [ABSTRACT FROM AUTHOR]

Water reuse programs are being explored to close the gap between supply and demand for irrigation in agriculture. However, these sources could contain hazardous microbial contaminants, and pose risks to public health. This study aimed to grow and irrigate romaine lettuce with inoculated wastewater effluent to track AP205 bacteriophage prevalence through cultivation and post-harvest storage. AP205 is a bacteriophage and was used as a surrogate for enteric viruses. Low and high dosages (mean ± standard deviation) of AP205 at 4.8 ± 0.4 log PFU/mL and 6.6 ± 0.2 log PFU/mL; respectively, were prepared to examine viral load influence on contamination levels. Foliage, leachate, and soil contamination levels were directly related to AP205 concentrations in the effluent. AP205 concentrations increased throughout cultivation for foliage and leachate, suggesting bacteriophage accumulation. During post-harvest storage (14 day at 4 °C), there was a significant decrease in AP205 concentration on the foliage. Results show that wastewater effluents usage for leafy greens cultivation can pose risks to humans and additional steps are required to safely apply wastewater effluents to soils and crops. [ABSTRACT FROM AUTHOR]

Summary: This paper explores use of metrics that combine fracture outcomes that add power to phase 3 studies and provide a surrogate outcome for regulatory agencies. Introduction: The aim of this study was to develop an analytic framework that would combine information from all fracture outcomes (including radiographic vertebral fractures) in phase 3 studies to provide a metric for the assessment of treatment efficacy. Methods: Data from the phase 3 study of denosumab were used as an exemplar comparing the effects of active intervention with placebo on the risk of all fractures associated with osteoporosis. Fracture outcomes were assigned utility weights drawn from the published literature and applied to age-specific health state values of the general population. For each fracture outcome in each arm of the study, cumulative disutility was computed to serve as the principal end point. The hypothesis tested was that treatment with denosumab results in a significant reduction in mean fracture-related disutility. Results: Treatment with denosumab was associated with significantly lower utility loss compared with placebo. For patients treated with denosumab, mean utility loss was 42% less than with placebo (4.5 vs. 7.5 QALYs/1000 patient years, respectively, p < 0.001). Conclusions: Denosumab significantly decreased utility loss. The use of metrics that combine fracture outcomes may provide added power to phase 3 studies and provide a surrogate outcome for regulatory agencies. [ABSTRACT FROM AUTHOR]

Summary: The COVID-19 pandemic, and its management, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, access was 58% lower in April than in February 2020. Strategies to improve osteoporosis care, with greater use of fracture risk assessments, offer a partial solution. Introduction: The COVID-19 pandemic is having a significant detrimental impact on the management of chronic diseases including osteoporosis. We have quantified the global impact by examining changes in the usage of online FRAX fracture risk assessments before and after the declaration of the pandemic (11 March 2020). Methods: The study comprised a retrospective analysis using GoogleAnalytics data on daily sessions on the FRAX® website (www.sheffield.ac.uk/FRAX) from November 2019 to April 2020 (main analysis period February–April 2020), and the geographical source of that activity. Results: Over February–April 2020, the FRAX website recorded 460,495 sessions from 184 countries, with 210,656 sessions in February alone. In March and April, the number of sessions fell by 23.1% and 58.3% respectively, a pattern not observed over the same period in 2019. There were smaller reductions in Asia than elsewhere, partly related to earlier and less-marked nadirs in some countries (China, Taiwan, Hong Kong, South Korea and Vietnam). In Europe, the majority of countries (24/31, 77.4%) reduced usage by at least 50% in April. Seven countries showed smaller reductions (range − 2.85 to − 44.1%) including Poland, Slovakia, Czech Republic, Germany, Norway, Sweden and Finland. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. Conclusion: This study documents a marked global impact of the COVID-19 pandemic on the management of osteoporosis as reflected by FRAX online fracture risk assessments. The analysis suggests that impact may relate to the societal and healthcare measures taken to ameliorate the pandemic. [ABSTRACT FROM AUTHOR]

This pilot study's goal was to investigate the impacts of static magnetic fields (SMF) on finger skin blood perfusion (SBP) when exposing the ulnar artery and ulnar and medial nerves to a rare earth concentric magnet for 30 minutes. Control SBP was measured in 4th fingers of adults (n = 12, age 26.0 ± 1.4 years) for 15 minutes using laser-Doppler. Then, active-magnets were placed over one arm's ulnar and median nerves at the wrist and sham-magnets placed at corresponding sites on the other arm. Devices were randomly assigned and placed by an investigator "blinded" to device type. The maximum SMF perpendicular to skin was 0.28 T measured 2 mm from magnet surface. The tangential field at this distance was 0.20 T. SBP was analyzed and tested for differential effects attributable to magnets compared to shams in each of the 5-minute intervals over the full 45-minute experiment. Results showed no statistically significant difference between SBP measured on the magnet-treated side compared to the sham side. Magnet and sham side SBP values (mean ± SEM, arbitrary units) prior to device placement were 0.568 ± 0.128 vs. 0.644 ± 0.115, p =.859 and during device placement were 0.627 ± 0.135 vs. 0.645 ± 0.117, p =.857. In conclusion, these findings have failed to uncover any significant effects of the static magnetic field on skin blood perfusion in the young healthy adult population evaluated. Its potential for altering SBP in more mature persons or those with underlying conditions affecting blood flow has not been evaluated but represents the next target of research inquiry. ClinicalTrials.gov registration number is NCT04539704. [ABSTRACT FROM AUTHOR]

This study investigated impacts of local skin heating on skin properties and tested whether skin changes depended on heat‐induced hyperaemia. It was reasoned that heat‐induced vasodilation impacts accompanying interstitial fluid changes. Forearm skin was locally heated from a baseline of 35°C to 40–42°C in 30 young adults (15 females, 15 males, 24.9 ± 2.1 years) and non‐heated in 10 others (5 females, 5 males, 25.2 ± 1.3 years. Skin blood flow (SBF) was continuously measured using a laser Doppler method and skin tissue dielectric constant (TDC), stratum corneum capacitance (SCC) and transepidermal water loss (TEWL) were measured before and after maintained heat for 12 min. TDC values were determined to effective measurement depths of 1.5 mm (TDC15) and 2.5 mm (TDC25). Results showed a large heat‐induced hyperaemia, with SBF increasing on average 8.8‐fold from its baseline of 35°C. Heating also caused significant increases in TDC, SCC and TEWL that, compared to preheating, increased approximately 1.1‐fold, 3.1‐fold and 4.5‐fold. None of these skin changes correlated with the magnitude of the SBF hyperaemic response. Absence of this correlation may indicate that in young healthy adults, increased capillary filtration due to heat‐induced arteriolar vasodilation is rapidly accommodated by postcapillary reabsorption, enhanced lymphatic activity and TEWL processes. An alternate explanation is that heating caused increased red cell oscillations that were detected as part of the laser Doppler increase without representing increased capillary flux. The major determinant of the Increases in TDC, SCC and TEWL is likely a consequence of heat‐induced eccrine gland activation. Studies of older persons or those with depressed function are warranted. [ABSTRACT FROM AUTHOR]

Objective Following breast cancer surgery with lymph node removal, women are at risk of developing lymphedema in the upper extremity or trunk. Currently, trunk lymphedema diagnosis relies on a clinical assessment because no quantifiable standard method exists. Tissue dielectric constant (TDC) values are quantifiable measures of localized skin tissue water and may be able to detect trunk lymphedema. The goal of this study was to (1) compare parameters derived from TDC measurements with those derived from clinically accepted criteria for trunk lymphedema in women following breast cancer surgery and (2) explore the potential utility of TDC to detect trunk lymphedema early in its progression. Methods This prospective longitudinal study, a secondary analysis from a larger study, observed women with and without clinically determined truncal lymphedema following breast cancer surgery. TDC was measured on the lateral trunk wall at post-surgery weeks 2, 4, 12, and 78 in women who had surgical breast cancer treatment with lymph node removal. Clinical assessment for trunk lymphedema was determined at 78 weeks by a lymphedema expert. Comparison of TDC measurements in women with and without clinical trunk lymphedema was analyzed. Results Clinical assessment identified trunk lymphedema in 15 out of 32 women at 78 weeks. These women had TDC ratios statistically higher than women without truncal lymphedema. Conclusion The overall findings indicate that TDC has the ability to quantify trunk lymphedema and might be valuable in early detection. Impact TDC may be a beneficial tool in the early detection of breast cancer–related trunk lymphedema, which could trigger intervention. Lay Summary A new device may help recognize trunk lymphedema in patients with breast cancer so they could receive appropriate treatment. [ABSTRACT FROM AUTHOR]

Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n = 62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but eight nuclear encoded variants in seven separate genes were found to be associated with exercise responses (FDR < 0.05) (rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2). Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities. [ABSTRACT FROM AUTHOR]

Summary: The impact of 20 min of whole‐body heating (WBH) on the tissue dielectric constant (TDC) of forearm and hand skin was evaluated in 24 young adults. TDC was measured in triplicate at 300 MHz using an open‐ended transmission line method in which the effective measurement depth was about 2 mm. TDC measurements are an effective way to assess and track localized oedema and lymphoedema. The underlying hypothesis was that heat‐induced eccrine gland activation would increase TDC values via an increase in fluid within the TDC measurement volume. The goal was to test this concept and to determine the magnitude of the change when environmental temperatures were elevated to near 42°C and to estimate TDC recovery time. The practical aspect of this research is motivated by the fact that patients in whom such measurements are made may arrive at the clinic in various states of sweat gland activation. Thus, knowledge of the effect of such activation on measured TDC values permits better understanding of possible relationships between such activation and TDC values. Results showed that increasing environmental temperature from 23·3 ± 1·6 to 41·5 ± 1·3°C increased forearm and thenar eminence skin temperatures to 37·8 ± 0·5 and 37·9 ± 0·4°C, respectively. These changes were associated with increases in TDC at arm from 30·7 ± 4·6 to 36·3 ± 5·7 (18·2%) and at hand from 34·7 ± 4·9 to 45·1 ± 5·5 (30%). Based on calculated TDC recovery rates, it is concluded that temperature‐related TDC variability can be minimized using a wait time of at least 15 min after bandage removal prior to TDC measurements in affected limbs. [ABSTRACT FROM AUTHOR]

Adaptation to exercise training is a complex trait that may be influenced by genetic variants. We identified 36 single nucleotide polymorphisms (SNPs) that had been previously associated with endurance or strength performance, exercise-related phenotypes or exercise intolerant disorders. A MassARRAY multiplex genotyping assay was designed to identify associations with these SNPs against collected endurance fitness phenotype parameters obtained from two exercise cohorts (Gene SMART study; n = 58 and Hawaiian Ironman Triathlon 2008; n = 115). These parameters included peak power output (PP), a time trial (TT), lactate threshold (LT), maximal oxygen uptake (VO2 max) in recreationally active individuals and a triathlon time-to-completion (Hawaiian Ironman Triathlon cohort only). A nominal significance threshold of α < 0.05 was used to identify 17 variants (11 in the Gene SMART population and six in the Hawaiian Ironman Triathlon cohort) which were significantly associated with performance gains in highly trained individuals. The variant rs1474347 located in Interleukin 6 (IL6) was the only variant with a false discovery rate < 0.05 and was found to be associated with gains in VO2 max (additional 4.016 mL/(kg min) for each G allele inherited) after training in the Gene SMART cohort. In summary, this study found further evidence to suggest that genetic variance can influence training response in a moderately trained cohort and provides an example of the potential application of genomic research in the assessment of exercise trait response. [ABSTRACT FROM AUTHOR]

Background: Skin tissue dielectric constant (TDC) measurements at a frequency of 300 MHz are used to assess skin properties in many conditions. Impacts of patient obesity on these values are unknown, and its quantitative assessment was the goal of this research. Materials and Methods: Women in a weight loss program (N = 32) had TDC measured on forearm, biceps, neck, jowl, and submental regions along with measurements of total body fat (TBF), water (TBW), intracellular water (ICW), and extracellular water (ECW) via multi‐frequency bioimpedance. Group age (mean ± SD) was 40.0 ± 11.6 years (20‐70 years) with body mass index (BMI) of 31.8 ± 6.7 Kg/m2 (23.0‐49.9 Kg/m2). For analysis, subjects were divided into those with BMI < 30 Kg/m2 (subgroup A, n = 16) vs ≥30 Kg/m2 (subgroup B, n = 16). Results: Tissue dielectric constant at forearm and biceps decreased significantly (P <.001) with increasing depth from 0.5 to 1.5 to 2.5 mm but TDC values and their inter‐side ratios did not differ between subgroups A and B at any measured site. Although correlations between TBW, ECW, and ICW were significant (P <.001), there was no dependence of TDC values on any of these parameters. Conclusions: Previously unknown TDC values for obese persons are provided and based on subgroup analyses suggest that skin TDC values in overweight and obese persons are not confounded by variables such as TBW and TBF. Further, since inter‐side ratios and their SD's yielded thresholds for forearm and biceps similar to those established for women with normal BMI, use of these clinical inter‐arm TDC ratios now is extended to include a wider BMI range. [ABSTRACT FROM AUTHOR]

Summary: Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods: Clinical perspective and updated literature search. Results: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions. [ABSTRACT FROM AUTHOR]

Summary: In the large community-based SCOOP trial, systematic fracture risk screening using FRAX® led to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care. Introduction: In the SCreening of Older wOmen for Prevention of fracture (SCOOP) trial, we investigated the effect of the screening intervention on subsequent long-term self-reported adherence to anti-osteoporosis medications (AOM). Methods: SCOOP was a primary care–based UK multicentre trial of screening for fracture risk. A total of 12,483 women (70–85 years) were randomised to either usual NHS care, or assessment using the FRAX® tool ± dual-energy X-ray absorptiometry (DXA), with medication recommended for those found to be at high risk of hip fracture. Self-reported AOM use was obtained by postal questionnaires at 6, 12, 24, 36, 48 and 60 months. Analysis was limited to those who initiated AOM during follow-up. Logistic regression was used to explore baseline determinants of adherence (good ≥ 80%; poor < 80%). Results: The mean (SD) age of participants was 75.6 (4.2) years, with 6233 randomised to screening and 6250 to the control group. Of those participants identified at high fracture risk in the screening group, 38.2% of those on treatment at 6 months were still treated at 60 months, whereas the corresponding figure for the control group was 21.6%. Older age was associated with poorer adherence (OR per year increase in age 0.96 [95% CI 0.93, 0.99], p = 0.01), whereas history of parental hip fracture was associated with greater rate adherence (OR 1.67 [95% CI 1.23, 2.26], p < 0.01). Conclusions: Systematic fracture risk screening using FRAX® leads to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care. [ABSTRACT FROM AUTHOR]

The implementation and popularity of next generation sequencing (NGS) has led to the development of various rapid whole mitochondrial genome sequencing techniques. We summarise an efficient and cost-effective NGS approach for mitochondrial genomic DNA in humans using the Ion Torrent platform, and further discuss our bioinformatics pipeline for streamlined variant calling. Ion 316 chips were utilised with the Ion Torrent semi-conductor platform Personal Genome Machine (PGM) to perform tandem sequencing of mitochondrial genomes from the core pedigree (n = 315) of the Norfolk Island Health Study. Key improvements from commercial methods focus on the initial PCR step, which currently requires extensive optimisation to ensure the accurate and reproducible elongation of each section of the complete mitochondrial genome. Dual-platform barcodes were incorporated into our protocol thereby extending its potential application onto Illumina-based systems. Our bioinformatics pipeline consists of a modified version of GATK best practices tailored for mitochondrial genomic data. When compared with current commercial methods, our method, termed high throughput mitochondrial genome sequencing (HTMGS), allows high multiplexing of samples and the use of alternate library preparation reagents at a lower cost per sample (~1.7 times) when compared to current commercial methodologies. Our HTMGS methodology also provides robust mitochondrial sequencing data (>450X average coverage) that can be applied and modified to suit various study designs. On average, we were able to identify ~30 variants per sample with 572 variants observed across 315 samples. We have developed a high throughput sequencing and analysis method targeting complete mitochondrial genomes; with the potential to be platform agnostic with analysis options that adhere to current best practices. [ABSTRACT FROM AUTHOR]

Purpose: Significant post-operative pain occurs after hip arthroplasty. In a prior study, lumbar plexus nerve blocks provided comparable analgaesia to lumbar epidurals; however, multimodal analgaesics were not used consistently.Methods: This study assessed a randomly selected cohort of 48 patients undergoing primary hip arthroplasty who received a regional anaesthesia technique for post-operative pain. Twenty-four patients with lumbar epidurals and 24 with single-injection lumbar plexus nerve blocks were reviewed using electronic medical records. Post-operative opiate consumption was the primary endpoint. Secondary endpoints were participation in physical therapy, side effects, and time to discharge. Descriptive statistics were calculated to describe patients in the different groups. Opiate consumption was compared using linear mixed models. Multivariable models were examined for both primary and secondary endpoints.Results: In comparison with patients receiving lumbar epidural catheters, patients with lumbar plexus blocks consumed less opiates post-operatively at 24-36 and 36-48 hours (P = 0.037 and 0.002, respectively); it did not differ at zero to 12 hours or 12-24 hours post-operatively. Patients with lumbar plexus blocks had earlier times to first ambulation (28.5 ± 3.29 vs 21.9 ± 1.76 h; P = 0.043). However, differences by block type were not observed for ambulation distance, level of assistance to ambulate or time of discharge orders.Conclusions: Following primary total hip arthroplasty, lumbar plexus nerve blocks provide effective post-operative analgaesia with decreased opiate consumption compared with lumbar epidural catheters. Lumbar plexus blocks also promote earlier post-operative ambulation and are compatible with post-operative prophylactic anticoagulants. [ABSTRACT FROM AUTHOR]

Summary: Inter‐arm systolic blood pressure differences (SBP‐DIFF) ≥ 10 mmHg have been reported useful to predict future cardiovascular‐related morbidities. Although well studied in patients, there is little information on healthy young adults and the role of hand‐dominance as a factor affecting SBP‐DIFF. As dominant arms (DOM) tend to have greater girth and muscle development than nondominant arms (NDOM) it was reasoned that cuff pressures needed to obtain SBP may be greater on DOM causing DOM SBP to be greater. To test this hypothesis and also provide typical values, SBP was measured in left and right‐handers (29·4 ± 10·4 years) in whom handedness was clearly defined. Handedness was determined by a multi‐question form in 90 young adults (45 male) and SBP‐DIFF determined via simultaneous measurements done in triplicate on seated subjects. The percentage of left‐handers in male and female sub‐groups were equal at 37·8%. Results show that the absolute SBP‐DIFF in left‐handers (mean ± SD) was 4·4 ± 3·8 mmHg and for right‐handers was 5·0 ± 4·2 mmHg (P = 0·362). There was also no statistically significant difference among 1st, 2nd and 3rd measured SBP‐DIFF for either right or left‐handers or differences between right and left‐handers. Results show no evidence of a higher SBP in DOM and thus clarifies the hand‐dominance issue as a factor not generally needing to be considered in clinical assessments. A potentially useful secondary outcome was the finding that 14·8% of this group had at least one measured SBP‐DIFF ≥ 10 mmHg a fact that may have future relevance. [ABSTRACT FROM AUTHOR]

Summary: Background: Quantitative assessment of possible linkages between skin's firmness and water content is useful for cosmetic and clinical purposes and to better understand features of advancing age. Objectives: Our goals were to characterize age‐related differential features in skin firmness in women and determine the relationship between skin firmness and indices of skin water. Methods: Skin firmness was quantified using handheld devices that measure the force to indent skin 0.3 and 1.3 mm (F0.3 and F1.3). Skin hydration was quantified using handheld devices that measured tissue dielectric constant (TDC) at 300 MHz to skin depths of 0.5 and 2.0‐2.5 mm. All parameters were measured bilaterally in the jowl area and volar forearm of 60 women grouped by age <45 years (YOUNG) and ≥45 years old (MATURE). Results: All measured parameters were bilaterally symmetrical at jowl and forearm. Forearm and jowl indentation forces were greater in YOUNG with statistically significant declines with advancing age with regression relations most evident at shallower indentation depths (P <.001). Quantitative relations for arm and jowl were F0.3 = 0.256 × AGE + 32.7 mN and F0.3 = −0.07 × AGE + 17.7 mN. Firmness was related to TDC values only when indentation force and TDC were assessed on the arm at the shallowest skin depths, as weakly related to firmness and was observed to change with age only when measured to a depth of 0.5 mm represented by TDC5 = 0.096 × AGE + 32.7. Conclusions: Experimental finding show clear differences in skin firmness between age‐groups with skin hydration playing a minor role. Possible explanations and suggestions for further studies are provided. [ABSTRACT FROM AUTHOR]

Summary: skin tissue dielectric constant (TDC) measurements help assess local skin water to detect incipient early‐stage lymphedema subsequent to breast cancer treatment‐related lymphedema. However, presurgery measurements are not always obtained and assessments for evolving lymphedema are only made after surgery. Thus, subsequent TDC assessments may be biased in an unknown way dependent on a patient's handedness in relation to the at‐risk arm. We investigated this issue by comparing TDC values in dominant and non‐dominant volar forearms of 31 left‐handed women and 31 right‐handed women (age range 24–84 years). Body fat and water percentages were assessed by bioimpedance at 50 KHz. Results showed that TDC values of dominant versus non‐dominant arms did not significantly differ for left‐handers or for right‐handers. There was also no statistically significant difference in absolute TDC values between left‐ and right‐handers or a statistically significant difference in dominant‐to‐non‐dominant arm ratios between left‐ and right‐handers. For the composite data set (N = 62), TDC values for dominant and non‐dominant arms were, respectively, 30·0 ± 4·6 and 29·6 ± 4·2 and the dominant‐to‐non‐dominant arm TDC ratio for combined left‐ and right‐handers was 1·015 ± 0·075. These results suggest that handedness is not a major factor when assessing lymphedema status in women who have previously been treated for breast cancer but for whom pretreatment TDCvalues have not been obtained. Moreover, these results suggest that threshold ratios of incipient subclinical unilateral lymphedema based on interarm TDC ratios apply independent of a patient's handedness for the site and tissue depths herein measured. [ABSTRACT FROM AUTHOR]

Discusses mining in Leadville, Colorado. Zinc mining; Discovery of placer gold in the 1860s; G.F. Loughlin, of the United States Geological Survey; Zinc deposits in the US; The Hayden Survey in Colorado; The Empire Zinc Company; The Hilltop Mine; The Meadville Mining Company; The erection of roasting furnaces at Leadville in 1883; Walter Renton Ingalls, a noted authority on lead and zinc; Carbonate ores; More.

Pareto front from multi-objective MOSCEM calibration (circle) and validation (triangle) using streamflow (Q) and evapotranspiration (ET) or Q and leaf area index (LAI). The variance of residuals (predicted – observed) for log-transformed Q is plotted against the variance of residuals for ET or LAI. The colour gradient is based on the variance of residuals for Q during calibration (i.e. blue points have low variance of residuals for Q, whereas red dots are associated with high values). The colours are kept consistent during validation, allowing for the shift of points to be observed. The labelled calibration points correspond to the validation points outlined in black (some overlap present). These points were deemed 'superior' due to their inclusion in the calibration Pareto front and their relative proximity to the origin during validation (i.e. lowest variance of residuals during both calibration and validation). [Display omitted] • Data type and model structure influence the Pareto front. • Performance of Pareto front solutions vary between calibration and validation. • Model structural deficiencies are revealed by multi-objective validation. • Multi-objective calibration with two flux variables improves model performance. • Identifying one optimal parameter set from a Pareto set remains elusive. Calibrating a hydrological model using more than one independent data set (multi-objective calibration) can potentially improve parameter estimation. However, it often identifies multiple parameter sets whose combined performance is generally indistinguishable, as visualized via a Pareto front. The objective of this paper is to identify how Pareto optimal solutions perform during model validation, and to identify how objective function tradeoffs in calibration might shift along the Pareto front during validation. Model calibration was based on an ecohydrological model simulating leaf area index (LAI), evapotranspiration (ET) and streamflow. Focusing on a predominantly forested Australian catchment and using satellite derived LAI and ET with observed streamflow for calibration, gave understanding of differences in model behavior related to observed data. The performance shifts between validation and calibration periods were assessed for combinations of ET and streamflow and LAI and streamflow. For both observed data combinations the performance deteriorated between calibration to validation and the "best" performing validation parameter solutions were scattered along the calibration Pareto front. In general, the streamflow/LAI data pairing showed a greater deterioration in streamflow performance in validation compared to the streamflow/ET data pairing. However, in both cases there was significant parameter equifinality. The results highlight that model structural limitations are a greater issue for model validation performance than in calibration. The identification of one optimal parameter set from a Pareto set remains elusive. [ABSTRACT FROM AUTHOR]

Volcanic ash poses an ongoing risk to safety in the airspace worldwide. The accuracy with which volcanic ash dispersion can be forecast depends on the conditions of the atmosphere into which it is emitted. In this study, meteorological ensemble forecasts are used to drive a volcanic ash transport and dispersion model for the 2010 Eyjafjallajökull eruption in Iceland. From analysis of these simulations, the authors determine why the skill of deterministic-meteorological forecasts decreases with increasing ash residence time and identify the atmospheric conditions in which this drop in skill occurs most rapidly. Large forecast errors are more likely when ash particles encounter regions of large horizontal flow separation in the atmosphere. Nearby ash particle trajectories can rapidly diverge, leading to a reduction in the forecast accuracy of deterministic forecasts that do not represent variability in wind fields at the synoptic scale. The flow-separation diagnostic identifies where and why large ensemble spread may occur. This diagnostic can be used to alert forecasters to situations in which the ensemble mean is not representative of the individual ensemble-member volcanic ash distributions. Knowledge of potential ensemble outliers can be used to assess confidence in the forecast and to avoid potentially dangerous situations in which forecasts fail to predict harmful levels of volcanic ash. [ABSTRACT FROM AUTHOR]

This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into four distinct themes: (1) case finding and management of individuals at high risk of fracture, (2) public awareness of osteoporosis and fragility fractures, (3) reimbursement and health system policy and (4) epidemiology of fracture in the developing world. Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits, are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all. Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health and people who have diseases, whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored. Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment. With regard to prioritisation of fragility fracture prevention in national policy, there is much to be done. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development. As the aging of the baby boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all. [ABSTRACT FROM AUTHOR]

Prior research suggests that tissue dielectric constant ( TDC) values are useful to assess localized skin water in females for early diagnosing breast cancer treatment-related lymphoedema and TDC values in young adults have shown gender differences. However, no TDC data are available for older males nor have ageing effects been studied despite known shifts in water state and other skin age-related changes. Thus our goals were to (i) characterize TDC values at various skin depths in young and older males, (ii) determine the dependence of these values on body composition parameters and (iii) establish inter-arm TDC ratios for use as normal male reference values. TDC measurements were made to depths of 0·5, 1·5, 2·5 and 5·0 mm bilaterally on volar forearm skin in 60 males in three groups of 20 that had mean ages ± SD of 24·0 ± 0·9, 40·0 ± 12·9 and 71·0 ± 8·0 years. Total body fat and water percentages were determined via bioimpedance at 50 KHz. Results showed that (i) for all age groups TDC values decreased with increasing depth, (ii) TDC values were not statistically different among age groups except at a depth of 0·5 mm, (iii) TDC values were highly negatively correlated with total body fat and (iv) inter-arm ratios varied little among age groups and depths. It is concluded that (i) age-related larger TDC values at only the shallowest depth is consistent with skin water shifting state from bound to more mobile in the oldest group and (ii) inter-arm ratios at any depth provide a basis to test for unilateral oedema. [ABSTRACT FROM AUTHOR]

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose Our goal was to test the hypothesis that skin firmness correlates with skin hydration. Methods Dermal water was assessed by tissue dielectric constant ( TDC) at 0.5 mm ( TDC0.5) and 2.5 mm ( TDC2.5) depths on four face sites and two arm sites of 35 women (25.0 ± 1.6 years). Firmness was determined by force ( mN) to indent skin to 0.3 mm (F0.3) and 1.3 mm (F1.3). Results F0.3 was similar among face sites (avg = 16.2 ± 7.2 mN) but F1.3 varied (avg = 32.5 ± 4.1 mN). TDC2.5 was similar among face sites (avg = 37.7 ± 4.2) but TDC0.5 varied (avg = 36.2 ± 4.8). F1.3 of arm sites was similar (avg = 60.2 ± 18.6 mN) and both greater than F1.3 of neck (28.3 ± 7.1 mN) and face. Regression analysis showed a near-zero correlation between forces and TDC at all sites. Conclusion The near-zero correlation may be due to low skin interstitial hydraulic resistance to mobile water movement in healthy young skin. If true, then conditions in which dermal hydraulic conductance is reduced as in lymphedematous, diabetic, or aged skin are more likely show the hypothesized relationship. Our findings provide normalized reference values and suggest that such persons are an important population to study to test for a possible skin water-indentation force relationship and its utilization for early diagnosis. [ABSTRACT FROM AUTHOR]

A correction to the article "Elevated blood pressure, antihypertensive medications and bone health in the population: revisiting old hypotheses and exploring future research directions" is presented which appeared in the previous issue of the periodical.

Purpose: To comment on the latest technology appraisal of the National Institute for Clinical Excellence (NICE) in osteoporosis.Methods: Review of NICE Technology Appraisal (TA464) on bisphosphonate use in osteoporosis.Results: The NICE appraisal on bisphosphonate use in osteoporosis indicates that treatment with oral bisphosphonates may be instituted at a FRAX 10-year probability of major osteoporotic fracture above 1%. Implementation would mean that all women aged 50 years or older are deemed eligible for treatment, a position that would increase the burden of rare long-term side effects across the population.Conclusion: Cost-effectiveness thresholds for low-cost interventions should not be used to set intervention thresholds but rather to validate the implementation of clinically driven intervention thresholds. [ABSTRACT FROM AUTHOR]

Summary: Falls and fractures share several common risk factors. Although past falls is not included as an input variable in the FRAX calculator, we demonstrate that FRAX probability predicts risk of incident falls in the MrOs Sweden cohort. Introduction: Although not included in the FRAX® algorithm, it is possible that increased falls risk is partly dependent on other risk factors that are incorporated into FRAX. The aim of the present study was to determine whether fracture probability generated by FRAX might also predict risk of incident falls and the extent that a falls history would add value to FRAX. Methods: We studied the relationship between FRAX probabilities and risk of falls in 1836 elderly men recruited to the MrOS study, a population-based prospective cohort of men from Sweden. Baseline data included falls history, clinical risk factors, bone mineral density (BMD) at femoral neck, and calculated FRAX probabilities. Incident falls were captured during an average of 1.8 years of follow-up. An extension of Poisson regression was used to investigate the relationship between FRAX, other risk variables, and the time-to-event hazard function of falls. All associations were adjusted for age and time since baseline. Results: At enrolment, 15.5 % of the men had fallen during the preceding 12 months (past falls) and 39 % experienced one or more falls during follow-up (incident falls). The risk of incident falls increased with increasing FRAX probabilities at baseline (hazard ratio (HR) per standard deviation (SD), 1.16; 95 % confidence interval (95%CI), 1.06 to 1.26). The association between incident falls and FRAX probability remained after adjustment for past falls (HR per SD, 1.12; 95%CI, 1.03 to 1.22). High compared with low baseline FRAX score (>15 vs <15 % probability of major osteoporotic fracture) was strongly predictive of increased falls risk (HR, 1.64; 95%CI, 1.36 to 1.97) and remained stable with time. Whereas past falls were a significant predictor of incident falls (HR, 2.75; 95%CI, 2.32 to 3.25), even after adjustment for FRAX, the hazard ratio decreased markedly with increasing follow-up time. Conclusions: Although falls are not included as an input variable, FRAX captures a component of risk for future falls and outperforms falls history with an extended follow-up time. [ABSTRACT FROM AUTHOR]

The major application of FRAX in osteoporosis is to direct pharmacological interventions to those at high risk of fracture. Whereas the efficacy of osteoporosis treatment, with the possible exception of alendronate, is largely independent of baseline bone mineral density (BMD), it remains a widely held perception that osteoporosis therapies are only effective in the presence of low BMD. Thus, the use of FRAX in the absence of BMD to identify individuals requiring therapy remains the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high evidence-based validity to identify a risk responsive to intervention. The selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD and thus identifies a risk that is responsive to pharmacological intervention. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where facilities for BMD testing are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Thus concerns surrounding the use of FRAX in clinical practice without information on BMD are largely misplaced. [ABSTRACT FROM PUBLISHER]

Summary: Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here, we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. Introduction: Daily administration of 20 or 40 μg teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. Methods: One thousand six hundred thirty-seven postmenopausal women in the pivotal phase three trial, randomly assigned to receive placebo ( n = 544), teriparatide 20 μg per day ( n = 541) or teriparatide 40 μg per day ( n = 552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40 μg teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. Results: The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2 %. Treatment with teriparatide was associated with a 37 % decrease in all non-vertebral fractures (95 % CI 10-56 %) and a 56 % decrease in low-energy non-vertebral fractures (95 % CI 24-75 %) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66 % (95 % CI 50-77 %). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability ( p > 0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. Conclusion: We conclude that teriparatide significantly decreases the risk of non-vertebral and morphometric vertebral fractures in women by a similar extent, irrespective of baseline fracture probability. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to determine the efficacy of once-weekly teriparatide as a function of baseline fracture risk. Treatment with once-weekly teriparatide was associated with a statistically significant 79 % decrease in vertebral fractures, and in the cohort as a whole, efficacy was not related to baseline fracture risk. Introduction: Previous studies have suggested that the efficacy of some interventions may be greater in the segment of the population at highest fracture risk as assessed by the FRAX® algorithms. The aim of the present study was to determine whether the antifracture efficacy of weekly teriparatide was dependent on the magnitude of fracture risk. Methods: Baseline fracture probabilities (using FRAX) were computed from the primary data of a phase 3 study (TOWER) of the effects of weekly teriparatide in 542 men and postmenopausal women with osteoporosis. The outcome variable comprised morphometric vertebral fractures. Interactions between fracture probability and efficacy were explored by Poisson regression. Results: The 10-year probability of major osteoporotic fractures (without BMD) ranged from 7.2 to 42.2 %. FRAX-based hip fracture probabilities ranged from 0.9 to 29.3 %. Treatment with teriparatide was associated with a 79 % (95 % CI 52-91 %) decrease in vertebral fractures assessed by semiquantitative morphometry. Relative risk reductions for the effect of teriparatide on the fracture outcome did not change significantly across the range of fracture probabilities ( p = 0.28). In a subgroup analysis of 346 (64 %) participants who had FRAX probabilities calculated with the inclusion of BMD, there was a small but significant interaction ( p = 0.028) between efficacy and baseline fracture probability such that high fracture probabilities were associated with lower efficacy. Conclusion: Weekly teriparatide significantly decreased the risk of morphometric vertebral fractures in men and postmenopausal women with osteoporosis. Overall, the efficacy of teriparatide was not dependent on the level of fracture risk assessed by FRAX in the cohort as a whole. [ABSTRACT FROM AUTHOR]

Many studies evaluating model boundary-layer schemes focus on either near-surface parameters or short-term observational campaigns. This reflects the observational datasets that are widely available for use in model evaluation. In this article, we show how surface and long-term Doppler lidar observations, combined in such a way as to match model representation of the boundary layer as closely as possible, can be used to evaluate the skill of boundary-layer forecasts. We use a two-year observational dataset from a rural site in the UK to evaluate a climatology of boundary-layer type forecast by the UK Met Office Unified Model. In addition, we demonstrate the use of a binary skill score (Symmetric Extremal Dependence Index, SEDI) to investigate the dependence of forecast skill on season, horizontal resolution and forecast lead time. A clear diurnal and seasonal cycle can be seen in the climatology of both model and observations, with the main discrepancies being the model overpredicting cumulus-capped and decoupled stratocumulus-capped boundary layers and underpredicting well-mixed boundary layers. Using the SEDI skill score, the model is most skilful at predicting the surface stability. The skill of the model in predicting cumulus-capped and stratocumulus-capped stable boundary-layer forecasts is low, but greater than a 24 h persistence forecast. In contrast, the prediction of decoupled boundary layers and boundary layers with multiple cloud layers is lower than persistence. This process-based evaluation approach has the potential to be applied to other boundary-layer parametrization schemes with similar decision structures. [ABSTRACT FROM AUTHOR]

During growth, severe vitamin D deficiency in childhood can result in symptomatic hypocalcaemia and rickets. Despite the suggestion from some studies of a secular increase in the incidence of rickets, this observation may be driven more by changes in population demographics than a true alteration to age, sex and ethnicity-specific incidence rates; indeed, rickets remains uncommon overall and is rarely seen in fair-skinned children. Additionally, the impact of less severe vitamin D deficiency and insufficiency has received much interest in recent years, and in this review, we consider the evidence relating vitamin D status to fracture risk and bone mineral density (BMD) in childhood and adolescence. We conclude that there is insufficient evidence to support the suggestion that low serum 25-hydroxyvitamin D [25(OH)D] increases childhood fracture risk. Overall, the relationship between 25(OH)D and BMD is inconsistent across studies and across skeletal sites within the same study; however, there is evidence to suggest that vitamin D supplementation in children with the lowest levels of 25(OH)D might improve BMD. High-quality randomised trials are now required to confirm this benefit. [ABSTRACT FROM AUTHOR]

Summary: The incidence of clinical fractures and the associated factors were assessed in patients with systemic lupus erythematosus (SLE) versus matched controls. We found an increased fracture risk in SLE patients compared to controls. Glucocorticoid use, longer disease duration, neuropsychiatric disease complications and previous osteoporotic fractures were identified as associated factors. Introduction: The aims of this study were to estimate the risk of clinical fractures in patients with SLE versus matched controls and to evaluate the risk factors associated with clinical fractures in SLE. Methods: This is a population-based cohort study using the Clinical Practice Research Datalink (from 1987-2012). Each SLE patient ( n = 4,343) was matched with up to six controls ( n = 21,780) by age and sex. Clinical fracture type was stratified according to the WHO definitions into osteoporotic and non-osteoporotic fracture. Cox proportional hazards calculated relative rates (RR) of clinical fracture and time interaction terms to evaluate the timing patterns of fracture. Clinical fracture rates in SLE patients, stratified by age, gender, type of fracture, disease duration and therapy variables, were compared with those rates in controls. Results: Follow-up durations were 6.4 years in SLE patients and 6.6 years in controls. SLE patients had a 1.2-fold increased clinical fracture risk compared to controls (adjusted RR = 1.22, 95% CI = 1.05-1.42), and the risk further increased with a longer disease duration. Glucocorticoid (GC) use in the previous 6 months raised the risk of clinical fracture (adjusted RR = 1.27, 95% CI = 1.02-1.58). Cerebrovascular events, seizures and previous osteoporotic fractures were identified as predictors of clinical fractures. Conclusions: We found an increased risk of clinical fracture in SLE patients compared to controls. GC use in the previous 6 months and longer disease duration are associated with the increased fracture risk in SLE. Patients with neuropsychiatric organ damage or previous osteoporotic fractures are also at increased risk of the occurrence of clinical fractures. [ABSTRACT FROM AUTHOR]

Background Biophysical measures to assess that skin water includes stratum corneum hydration via capacitance ( SC), dermal water via tissue dielectric constant ( TDC), and transepidermal water loss ( TEWL). Since skin differs among anatomical sites and tissue depth we sought to determine the site and depth variability of these measures and their relationships. Methods Measurements were done at 17 skin sites from forehead to foot in 32 supine healthy women. Measurements included SC at 1.25 MHz, TDC at 300 MHz to depths of 0.5, 1.5, and 2.5 mm and TEWL. Results Tissue dielectric constant decreased with increasing depth at forehead, forearm, and calf; increased with depth at palm, thenar eminence and great toe; and was independent of depth at cheek, hand dorsum, thumb pulp, and foot dorsum. SC correlated with TDC at most sites and depths. TEWL correlated with TDC at 2.5 mm only at calf sites and thenar eminence. Conclusions Results establish parameter ranges for each measure, show that TDC values do not necessarily change with skin depth, and show a significant correlation between TDC and SC values at most sites. These correlations suggest that SC hydration but not TEWL is directly linked to dermal tissue water levels in normal skin. [ABSTRACT FROM AUTHOR]

Skin tissue dielectric constant ( TDC) values measured via the open-ended coaxial probe method are useful non-invasive indices of local skin tissue water. However, the effect of skin blood flow ( SBF) or skin blood volume ( SBV) on TDC values is unknown. To determine the magnitude of such effects, we decreased forearm SBV via vertical arm raising for 5 min (test 1) and increased SBV by bicep cuff compression to 50 mmHg for 5 min (test 2) in 20 healthy supine subjects (10 men). TDC values were measured to a depth of 1·5 mm on anterior forearm, and SBF was measured with laser-Doppler system simultaneously on forearm and finger. Results indicate that decreasing vascular volume (test 1) was associated with a small but statistically significant reduction in TDC (3·0 ± 4·3%, P = 0·003) and increasing vascular volume (test 2) was associated with a slight but statistically significant increase in TDC (3·5 ± 3·0%, P<0·001). SBF changes depended on test and measurement site. For forearm, test 1 significantly increased SBF (102·6 ± 156·2%, P<0·001) and test 2 significantly decreased it (39·5 ± 13·1%, P<0·001). In finger, SBF was significantly reduced by both tests: in test 1 by 55·3 ± 32·1%, P<0·001 and in test 2 by 53·3 ± 27·6%, P<0·001. We conclude that the small percentage changes in TDC values (3·0-3·5%) over the wide range of induced SBV and SBF changes suggest a minor effect on clinically determined TDC values because of SBV or SBF changes or differences when comparing TDC longitudinally over time or among individuals of different groups in a research setting. [ABSTRACT FROM AUTHOR]

Lateral table tilt or a pelvic wedge are commonly used to reduce inferior vena cava compression during obstetric anaesthesia in the supine position. Direct measurement of pelvic angle allows individual assessment of the effectiveness of these manoeuvres in achieving a tilted position. We observed routine practice during caesarean section after random allocation to one or other of these methods. The anaesthetist managing the case was asked to position the women after induction of spinal anaesthesia using either left table tilt or a wedge under the right hip. We then measured pelvic angle in all women, and the table angle in women who had table tilt. The mean (SD [range]) pelvic angle was 20.2° (8.1° [9°-37°]) in 18 women with table tilt and 21.0° (7.5° [10°-36°]) in 17 women with a wedge. The mean (SD [range]) table angle was 12.4° (3.1° [8°-21°]) in the women with table tilt. There was a significant difference between table angle and pelvic angle in the women with table tilt (p = 0.0003), but no significant difference in pelvic angle between the table tilt and wedge groups. Measurement of table angle does not represent pelvic position adequately in the majority of women. However, this study showed that lateral table tilt and a pelvic wedge were equally effective in producing tilt of the pelvis. [ABSTRACT FROM AUTHOR]

Background/purpose Skin tissue dielectric constant ( TDC) measurements at 300 MHz provide non-invasive data on free and bound tissue water. TDC-data is available for some body sites, but most is for female forearm. Contrastingly, there are no data on face-skin or comparative data between genders. Our goals were to obtain facial- TDC reference values and determine if TDC-values differ between genders. Methods TDC was measured at forehead, cheek, and forearm in 60 young adults (30 men) to a 1.5-mm depth. Measured TDC-values were compared with TDC-values calculated using skin-thickness data. Results Measured TDC-values ranged from 39.6 ± 2.9 at male-forehead to 28.2 ± 2.4 at female forearm and were significantly different ( P < 0.001) among each site in the order forehead > cheek >forearm. Male TDC-values were greater than female TDC-values ( P < 0.01) with differences from 5.6% at forehead to 11.3% at forearm. Calculated TDC-values incorporating site and gender skin-thickness differences yielded TDC-values at the most 3% different from measured values. Conclusion Gender differences should be considered in clinical studies in which men and women are included in a common study population with respect to experimental design and data interpretation. This is especially true if absolute TDC-values are of interest rather than changes in TDC-values on the same subject subsequent secondary to an intervention. [ABSTRACT FROM AUTHOR]

Summary: In this large, population-based, prospective, mother-offspring cohort study, maternal long chain polyunsaturated fatty acid (LCPUFA) status during pregnancy was found to be positively associated with bone mass in the offspring at age 4 years. The findings suggest that variation in intrauterine exposure to n-3 and n-6 LCPUFAs may have potential consequences for skeletal development. Introduction: Maternal diet in pregnancy has been linked to childhood bone mass, but the mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship between maternal fatty acid status and bone mass in the offspring remains unknown. Methods: We evaluated the association between maternal LCPUFA status in late pregnancy (34 weeks gestation) and bone density in their children at age 4 years within 727 mother-child pairs taking part in the Southampton Women's Survey. Results: Concentrations of the n-3 LCPUFA component of maternal plasma phosphatidylcholine were positively associated with a number of bone mineral measures at the age of 4 years; these associations persisted after adjustment for maternal body build, walking speed and infant feeding. Relationships were most evident for eicosapentaenoic acid ( r = 0.09, p = 0.02 for whole body areal bone mineral density [aBMD] and r = 0.1, p = 0.008 for lumbar spine aBMD) and for docosapentaenoic acid ( r = 0.09, p = 0.02 for whole body aBMD and r = 0.12, p = 0.002 for lumbar spine aBMD). Conclusions: These findings suggest that variation in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone development and that the effects appear to persist into early childhood. [ABSTRACT FROM AUTHOR]

Osteoporosis is a major public health problem due to consequent fragility fractures; data from the UK suggest that up to 50% of women and 20% men aged 50 years will have an osteoporosis-related fracture in their remaining lifetime. Skeletal size and density increase from early embryogenesis through intrauterine, infant, childhood and adult life to reach a peak in the third to fourth decade. The peak bone mass achieved is a strong predictor of later osteoporosis risk. Epidemiological studies have demonstrated a positive relationship between early growth and later bone mass, both at peak and in later life, and also with reduced risk of hip fracture. Mother-offspring cohorts have allowed the elucidation of some of the specific factors in early life, such as maternal body build, lifestyle and 25(OH)-vitamin D status, which might be important. Most recently, the phenomenon of developmental plasticity, whereby a single genotype may give rise to different phenotypes depending on the prevailing environment, and the science of epigenetics have presented novel molecular mechanisms which may underlie previous observations. This review will give an overview of these latter developments in the context of the burden of osteoporosis and the wider data supporting the link between the early environment and bone health in later life. [ABSTRACT FROM AUTHOR]

Summary: In a free-living cohort of 4-year old children, mean daily time in moderate-vigorous physical activity and daily calcium intake at 3 years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966 mg/day). Introduction: We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density. Methods: Children aged 4 years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days. Results: Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA ( R = 3%, p < 0.001), BMC ( R = 4%, p < 0.001), aBMD ( R = 3%, p = 0.001) and estimated vBMD ( R = 2%, p = 0.01), but not height ( r = 0.04, p = 0.42) or weight ( r = 0.01, p = 0.76). Mean daily calcium intake (assessed at 3 years old) positively predicted bone indices in those with a calcium intake below the median (966 mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% ( p = 0.1) and above median was 6% ( p = 0.001). Conclusions: These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass. [ABSTRACT FROM AUTHOR]

Survival in the everyday world (in both social and practical functioning) depends on one's ability to recognise and avoid going down the worst possible path, especially when doing so places one at risk of death, injury, or social disaster. Most people possess 'common sense' (the ability to recognise obvious risk) but some people lack that ability and thus are at high risk of engaging in 'foolish' (i.e., risk-unaware) action. People who have a cognitive impairment are much less able to recognise and avoid risk, and this is what causes them to be seen as needing protection and support. In this paper, we argue that the answer to the question 'What is intellectual disability (ID)?' is more likely to come from the question 'What is unintelligent behavior?' than 'What is intelligence?' The answer which comes from such a question is that 'ID is a common sense deficit disorder characterised by unawareness of obvious social and practical risk.' Several implications of this answer are explored for the field of intellectual disability. These implications are explored primarily for adults who may have ID, given that the inspiration for this paper came from the way existing ID definitions are applied or misapplied in the US adult criminal justice system. [ABSTRACT FROM AUTHOR]