Analysis of interdecadal variability of temperature extreme events in Argentina applying EVT

The frequency of occurrence of temperature extreme events has changed throughout the last century: significant positive trends in warm nights and negative trends in cold nights have been observed all over the world. In Argentina, the probability of occurrence of warm annual extremes of maximum temperature has decreased in the last decades, while there has been an increase in warm annual extremes of minimum temperature. The main objective of this paper is to evaluate observed interdecadal changes in the distribution of temperature events that exceed a fixed threshold in five meteorological stations from Argentina over the period 1941-2000, by applying the extreme value theory (EVT). The availability of daily data allows fitting a generalized Pareto distribution (GPD) to daily temperature anomalies over the 90th or below the 10th percentile, in order to estimate return values of extreme events. Daily temperature anomalies are divided into three consecutive and non-overlapping subperiods of 20 years. GPD is fitted to each subperiod independently and a comparison is made between return values estimated in each subperiod. Results show that there is a decrease in the intensity of warm extreme events during the whole period, together with anincrease in its frequency of occurrence during the last 20 years of the twentieth century. Cold extremes alsoshow a decrease in their intensity. However, changes in their frequency of occurrence are not so consistentbetween the different stations analyzed.La frecuencia de ocurrencia de los eventos extremos de temperatura ha sufrido variaciones a lo largo del último siglo: se han observado tendencias positivas significativas en las noches cálidas y tendencias negativas en las noches frías en todo el mundo. En Argentina, la probabilidad de ocurrencia de extremos cálidos anuales de la temperatura máxima disminuyó en las últimas décadas, mientras que hubo un incremento en la probabilidad de ocurrencia de extremos cálidos anuales de la temperatura mínima. El objetivo principal de este trabajo es evaluar la variabilidad interdecadal observada en la distribución de los eventos de temperatura que superan un determinado umbral en cinco estaciones meteorológicas de Argentina durante el periodo 1941-2000, mediante la aplicación de la teoría de valores extremos. La disponibilidad de datos diarios permite el ajuste de la distribución generalizada de Pareto (DGP) a las anomalías diarias de temperatura que exceden el percentil 90 o que no alcanzan el percentil 10 con el propósito de estimar los valores de retorno de los eventos extremos. Las series de anomalías diarias de temperatura se dividen en tres subperiodos consecutivos sin superposición de 20 años cada uno. La DGP se ajusta en cada uno de los tres subperiodos en forma independiente y se comparan los valores de retorno estimados en cada subperiodo. Los resultados muestran que hay una disminución en la intensidad de eventos extremos cálidos durante todo el periodo de estudio, junto con un incremento en su frecuencia de ocurrencia durante los últimos 20 años del siglo XX. Los extremos fríos también muestran una disminución en intensidad. Sin embargo, los cambios en su frecuencia de ocurrencia no son tan consistentes entre las diferentes estaciones estudiadas

The cost of severe haemophilia in Europe: the CHESS study

Background Severe haemophilia is associated with major psychological and economic burden for patients, caregivers, and the wider health care system. This burden has been quantified and documented for a number of European countries in recent years. However, few studies have taken a standardised methodology across multiple countries simultaneously, and sought to amalgamate all three levels of burden for severe disease. The overall aim of the ‘Cost of Haemophilia in Europe: a Socioeconomic Survey’ (CHESS) study was to capture the annualised economic and psychosocial burden of severe haemophilia in five European countries. A cross-section of haemophilia specialists (surveyed between January and April 2015) provided demographic and clinical information and 12-month ambulatory and secondary care activity for patients via an online survey. In turn, patients provided corresponding direct and indirect non-medical cost information, including work loss and out-of-pocket expenses, as well as information on quality of life and adherence. The direct and indirect costs for the patient sample were calculated and extrapolated to population level. Results Clinical reports for a total of 1,285 patients were received. Five hundred and fifty-two patients (43% of the sample) provided information on indirect costs and health-related quality of life via the PSC. The total annual cost of severe haemophilia across the five countries for 2014 was estimated at EUR 1.4 billion, or just under EUR 200,000 per patient. The highest per-patient costs were in Germany (mean EUR 319,024) and the lowest were in the United Kingdom (mean EUR 129,365), with a study average of EUR 199,541. As expected, consumption of clotting factor replacement therapy represented the vast majority of costs (up to 99%). Indirect costs are driven by patient and caregiver work loss. Conclusions The results of the CHESS study reflect previous research findings suggesting that costs of factor replacement therapy account for the vast majority of the cost burden in severe haemophilia. However, the importance of the indirect impact of haemophilia on the patient and family should not be overlooked. The CHESS study highlights the benefits of observational study methodologies in capturing a ‘snapshot’ of information for patients with rare diseases

Biomechanics of bone-fracture fixation by stiffness-graded plates in comparison with stainless-steel plates

BACKGROUND: In the internal fixation of fractured bone by means of bone-plates fastened to the bone on its tensile surface, an on-going concern has been the excessive stress-shielding of the bone by the excessively-stiff stainless-steel plate. The compressive stress-shielding at the fracture-interface immediately after fracture-fixation delays callus formation and bone healing. Likewise, the tensile stress-shielding of the layer of the bone underneath the plate can cause osteoporosis and decrease in tensile strength of this layer. METHOD: In order to address this problem, we propose to use stiffness-graded plates. Accordingly, we have computed (by finite-element analysis) the stress distribution in the fractured bone fixed by composite plates, whose stiffness is graded both longitudinally and transversely. RESULTS: It can be seen that the stiffness-graded composite-plates cause less stress-shielding (as an example: at 50% of the healing stage, stress at the fracture interface is compressive in nature i.e. 0.002 GPa for stainless steel plate whereas stiffness graded plates provides tensile stress of 0.002 GPa. This means that stiffness graded plate is allowing the 50% healed bone to participate in loadings). Stiffness-graded plates are more flexible, and hence permit more bending of the fractured bone. This results in higher compressive stresses induced at the fractured faces accelerate bone-healing. On the other hand, away from the fracture interface the reduced stiffness and elastic modulus of the plate causes the neutral axis of the composite structure to be lowered into the bone resulting in the higher tensile stress in the bone-layer underneath the plate, wherein is conducive to the bone preserving its tensile strength. CONCLUSION: Stiffness graded plates (with in-built variable stiffness) are deemed to offer less stress-shielding to the bone, providing higher compressive stress at the fractured interface (to induce accelerated healing) as well as higher tensile stress in the intact portion of the bone (to prevent bone remodeling and osteoporosis)

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study

BACKGROUND: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. METHODS: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd) of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 10(5 )colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). RESULTS: Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. CONCLUSION: ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD

Biomechanical evaluation of immediate stability with rectangular versus cylindrical interbody cages in stabilization of the lumbar spine

BACKGROUND: Recent cadaver studies show stability against axial rotation with a cylindrical cage is marginally superior to a rectangular cage. The purpose of this biomechanical study in cadaver spine was to evaluate the stability of a new rectangular titanium cage design, which has teeth similar to the threads of cylindrical cages to engage the endplates. METHODS: Ten motion segments (five L2-3, five L4-5) were tested. From each cadaver spine, one motion segment was fixed with a pair of cylindrical cages (BAK, Sulzer Medica) and the other with paired rectangular cages (Rotafix, Corin Spinal). Each specimen was tested in an unconstrained state, after cage introduction and after additional posterior translaminar screw fixation. The range of motion (ROM) in flexion-extension, lateral bending, and rotation was tested in a materials testing machine, with +/- 5 Nm cyclical load over 10 sec per cycle; data from the third cycle was captured for analysis. RESULTS: ROM in all directions was significantly reduced (p < 0.05) with both types of cages. There was no significant difference in reduction of ROM in flexion-extension (p = 0.6) and rotation (p = 0.92) between the two cage groups, but stability in lateral bending was marginally superior with the rectangular cages (p = 0.11). Additional posterior fixation further reduced the ROM significantly (p < 0.05) in most directions in both cage groups, but did not show any difference between the cage groups. CONCLUSIONS: There was no significant difference in immediate stability in any direction between the threaded cylindrical cage and the new design of the rectangular cage with endplate teeth

Development and evaluation of a tool for the assessment of footwear characteristics

<p>Abstract</p> <p>Background</p> <p>Footwear characteristics have been linked to falls in older adults and children, and the development of many musculoskeletal conditions. Due to the relationship between footwear and pathology, health professionals have a responsibility to consider footwear characteristics in the etiology and treatment of various patient presentations. In order for health professionals and researchers to accurately and efficiently critique an individual's footwear, a valid and reliable footwear assessment tool is required. The aim of this study was to develop a simple, efficient, and reliable footwear assessment tool potentially suitable for use in a range of patient populations.</p> <p>Methods</p> <p>Consideration of previously published tools, other footwear related literature, and clinical considerations of three therapists were used to assist in the development of the tool. The tool was developed to cover fit, general features, general structure, motion control properties, cushioning, and wear patterns. A total of 15 participants (who provided two pairs of shoes each) were recruited, and assessment using the scale was completed on two separate occasions (separated by 1 – 3 weeks) by a physiotherapist and a podiatrist on each participant's dominant foot. Intra-rater and inter-rater reliability were evaluated using intra-class correlation coefficients (ICCs) (model 2, 1) and the 95% limits of agreement (95% LOAs) for continuous items, and percentage agreement and kappa (κ) statistics for categorical items.</p> <p>Results</p> <p>All categorical items demonstrated high percentage agreement statistic for intra-rater (83 – 100%) and inter-rater (83 – 100%) comparisons. With the exception of last shape and objective measures used to categorise the adequacy of length, excellent intra-rater (ICC = 0.91 – 1.00) and inter-rater reliability (ICC = 0.90 – 1.00) was indicated for continuous items in the tool, including the motion control properties scale (0.91 – 0.95).</p> <p>Conclusion</p> <p>A comprehensive footwear assessment tool with good face validity has been developed to assist future research and clinical footwear assessment. Generally good reliability amongst all items indicates that the tool can be used with confidence in research and clinical settings. Further research is now required to determine the clinical validity of each item in various patient populations.</p

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction – A model for cross-modulation

<p>Abstract</p> <p>Background</p> <p>A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC.</p> <p>Methods</p> <p>PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome.</p> <p>Results</p> <p>When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk.</p> <p>Conclusion</p> <p>ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.</p

Efficacy of a multifaceted podiatry intervention to improve balance and prevent falls in older people: study protocol for a randomised trial

<p>Abstract</p> <p>Background</p> <p>Falls in older people are a major public health problem, with at least one in three people aged over 65 years falling each year. There is increasing evidence that foot problems and inappropriate footwear increase the risk of falls, however no studies have been undertaken to determine whether modifying these risk factors decreases the risk of falling. This article describes the design of a randomised trial to evaluate the efficacy of a multifaceted podiatry intervention to reduce foot pain, improve balance, and reduce falls in older people.</p> <p>Methods</p> <p>Three hundred community-dwelling men and women aged 65 years and over with current foot pain and an increased risk of falling will be randomly allocated to a control or intervention group. The "usual cae" control group will receive routine podiatry (i.e. nail care and callus debridement). The intervention group will receive usual care plus a multifaceted podiatry intervention consisting of: (i) prefabricated insoles customised to accommodate plantar lesions; (ii) footwear advice and assistance with the purchase of new footwear if current footwear is inappropriate; (iii) a home-based exercise program to strengthen foot and ankle muscles; and (iv) a falls prevention education booklet. Primary outcome measures will be the number of fallers, number of multiple fallers and the falls rate recorded by a falls diary over a 12 month period. Secondary outcome measures assessed six months after baseline will include the Medical Outcomes Study Short Form 12 (SF-12), the Manchester Foot Pain and Disability Index, the Falls Efficacy Scale International, and a series of balance and functional tests. Data will be analysed using the intention to treat principle.</p> <p>Discussion</p> <p>This study is the first randomised trial to evaluate the efficacy of podiatry in improving balance and preventing falls. The trial has been pragmatically designed to ensure that the findings can be generalised to clinical practice. If found to be effective, the multifaceted podiatry intervention will be a unique addition to common falls prevention strategies already in use.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry: ACTRN12608000065392</p