Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

Cumplimiento de las medidas de restricción del uso residencial de leña en la ciudad de Valdivia / Compliance with the measures of restrict the residential use of firewood in Valdivia, Chile

BACKGROUND: Atmospheric pollution is a problem that causes great concern and health risks for the population and the earth, as it affects developed countries and third world countries. Locally, there are no studies that prove the fulfillment level of the restriction about the usage of residential firewood, considering that since 2014 there is a procedure called "The Environmental Decontamination Plan" in Valdivia (PDAV). Aim: To determine the fulfillment level of the restriction about residential firewood and its related factors. MATERIAL AND METHODS: The population study were 594 homes that were assigned randomly and proportionally according to 2 territorial areas (A and B) established in the PDAV. The sample's characteristics were described, comparison techniques were applied by subgroups (sociodemographic, home's structures and humidity's perception and percentage of the firewood) to identify factors related mainly with the fulfillment of measurements about firewood usage. RESULTS: 52% of households do not comply with the residential firewood use restriction measure, having sociodemographic factors related with this failure, such as schooling, health insurance and home structure. Besides, it is noted that the knowledge level of PDAV is associated with the accomplish level of restriction measures. When people know more about PDAV, there is a higher proportion of accomplishment. Conclusion: In more than half of the households, the restriction on the use of woodstove is not complied. The lack of knowledge of the population about the PDAV directly influences its compliance, which requires strategies to promote adherence to this program.

[Compliance with the measures of restrict the residential use of firewood in Valdivia, Chile]. / Cumplimiento de las medidas de restricción del uso residencial de leña en la ciudad de Valdivia.

BACKGROUND: Atmospheric pollution is a problem that causes great concern and health risks for the population and the earth, as it affects developed countries and third world countries. Locally, there are no studies that prove the fulfillment level of the restriction about the usage of residential firewood, considering that since 2014 there is a procedure called "The Environmental Decontamination Plan" in Valdivia (PDAV). AIM: To determine the fulfillment level of the restriction about residential firewood and its related factors. MATERIAL AND METHODS: The population study were 594 homes that were assigned randomly and proportionally according to 2 territorial areas (A and B) established in the PDAV. The sample's characteristics were described, comparison techniques were applied by subgroups (sociodemographic, home's structures and humidity's perception and percentage of the firewood) to identify factors related mainly with the fulfillment of measurements about firewood usage. RESULTS: 52% of households do not comply with the residential firewood use restriction measure, having sociodemographic factors related with this failure, such as schooling, health insurance and home structure. Besides, it is noted that the knowledge level of PDAV is associated with the accomplish level of restriction measures. When people know more about PDAV, there is a higher proportion of accomplishment. CONCLUSION: In more than half of the households, the restriction on the use of woodstove is not complied. The lack of knowledge of the population about the PDAV directly influences its compliance, which requires strategies to promote adherence to this program.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

[Clinical and microbiological aspects of peritonitis associated with peritoneal dialysis in adult patients with chronic renal failure in the Emergency Department]. / Aspectos clínicos y microbiológicos de la peritonitis asociada a diálisis peritoneal en pacientes adultos con insuficiencia renal crónica en el Servicio de Urgencias.

BACKGROUND: Peritonitis is the most important and frequent complication of peritoneal dialysis (PD). Bacterial infections are responsible in most cases, with characteristic symptoms. AIM: To determine the most frequent pathogens in peritonitis associated with PD in patients with chronic renal failure (CRF). Methodos: Retrospective, descriptive, cross-sectional and observational study of patients with peritonitis in PD with CRF of the emergency department, between July 2012 and June 2013. Sociodemographic, diagnostic, clinical and microbiological and cellular data were evaluated from the patient's fluid. Dialysis. RESULTS: From 73 reviewed records, 52% were male. The primary cause of CRF was diabetes mellitus type 2 (67%). Symptoms presented: abdominal pain (86%), vomiting (42%) and nausea (34%), with anemia, azotemia, hyperglycemia, hypoalbuminemia and hyponatremia. The positive microbiological cultures were 59%; and the pathogens identified were Candida tropicalis (9.6%), Staphylococcus epidermidis (8.2%), Enterococcus faecalis and Staphylococcus haemolyticus (6.8% each one), associated with elevated leukocytes, azotemia and high cellularity in peritoneal fluid (p <0.05). CONCLUSIONS: The main microorganism determined was of fungal origin associated with leukocytes, azotemia and high cellularity.

In vitro and in vivo studies of the ALS-FTLD protein CHCHD10 reveal novel mitochondrial topology and protein interactions.

Mutations in coiled-coil-helix-coiled-coil-helix-domain containing 10 (CHCHD10), a mitochondrial twin CX9C protein whose function is still unknown, cause myopathy, motor neuron disease, frontotemporal dementia, and Parkinson's disease. Here, we investigate CHCHD10 topology and its protein interactome, as well as the effects of CHCHD10 depletion or expression of disease-associated mutations in wild-type cells. We find that CHCHD10 associates with membranes in the mitochondrial intermembrane space, where it interacts with a closely related protein, CHCHD2. Furthermore, both CHCHD10 and CHCHD2 interact with p32/GC1QR, a protein with various intra and extra-mitochondrial functions. CHCHD10 and CHCHD2 have short half-lives, suggesting regulatory rather than structural functions. Cell lines with CHCHD10 knockdown do not display bioenergetic defects, but, unexpectedly, accumulate excessive intramitochondrial iron. In mice, CHCHD10 is expressed in many tissues, most abundantly in heart, skeletal muscle, liver, and in specific CNS regions, notably the dopaminergic neurons of the substantia nigra and spinal cord neurons, which is consistent with the pathology associated with CHCHD10 mutations. Homozygote CHCHD10 knockout mice are viable, have no gross phenotypes, no bioenergetic defects or ultrastructural mitochondrial abnormalities in brain, heart or skeletal muscle, indicating that functional redundancy or compensatory mechanisms for CHCHD10 loss occur in vivo. Instead, cells expressing S59L or R15L mutant versions of CHCHD10, but not WT, have impaired mitochondrial energy metabolism. Taken together, the evidence obtained from our in vitro and in vivo studies suggest that CHCHD10 mutants cause disease through a gain of toxic function mechanism, rather than a loss of function.

Aspectos clínicos y microbiológicos de la peritonitis asociada a diálisis peritoneal en pacientes adultos con insuficiencia renal crónica en el Servicio de Urgencias / Clinical and microbiological aspects of peritonitis associated with peritoneal dialysis in adult patients with chronic renal failure in the Emergency Department

Resumen Introducción: La peritonitis es la complicación más importante y frecuente de la diálisis peritoneal (DP), las infecciones bacterianas son las responsables en la mayoría de los casos, con sintomatología característica. Objetivo: Determinar los patógenos más frecuentes en peritonitis asociado con la DP en pacientes con insuficiencia renal crónica (IRC). Metodología: Estudio retrospectivo, descriptivo, transversal y observacional, de pacientes con peritonitis en DP con IRC del servicio de urgencias, entre julio de 2012 y junio de 2013. Se evaluaron de los expedientes datos sociodemográficos, de diagnóstico, clínicos y microbiológicos y celulares de líquido de diálisis. Resultados: De 73 expedientes revisados 52% correspondían a pacientes del género masculino, la causa primaria de la IRC fue la diabetes mellitus tipo 2 (67%). Síntomas presentados: dolor abdominal (86%), vómitos (42%) y náuseas (34%), con anemia, azoemia, hiperglicemia hipoalbuminemia e hiponatremia. Los cultivos microbiológicos positivos fueron 59%; y los patógenos identificados fueron Candida tropicalis (9,6%), Staphylococcus epidermidis (8,2%), y Enterococcus faecalis y Staphylococcus haemolyticus (6,8% cada uno), asociados con elevación de leucocitos, azoemia y celularidad alta en el líquido peritoneal (p < 0,05). Conclusiones: El principal microorganismo determinado fue de origen fúngico asociado a leucocitos, azoemia y celularidad alta.

Background: Peritonitis is the most important and frequent complication of peritoneal dialysis (PD). Bacterial infections are responsible in most cases, with characteristic symptoms. Aim: To determine the most frequent pathogens in peritonitis associated with PD in patients with chronic renal failure (CRF). Methodos: Retrospective, descriptive, cross-sectional and observational study of patients with peritonitis in PD with CRF of the emergency department, between July 2012 and June 2013. Sociodemographic, diagnostic, clinical and microbiological and cellular data were evaluated from the patient's fluid. Dialysis. Results: From 73 reviewed records, 52% were male. The primary cause of CRF was diabetes mellitus type 2 (67%). Symptoms presented: abdominal pain (86%), vomiting (42%) and nausea (34%), with anemia, azotemia, hyperglycemia, hypoalbuminemia and hyponatremia. The positive microbiological cultures were 59%; and the pathogens identified were Candida tropicalis (9.6%), Staphylococcus epidermidis (8.2%), Enterococcus faecalis and Staphylococcus haemolyticus (6.8% each one), associated with elevated leukocytes, azotemia and high cellularity in peritoneal fluid (p <0.05). Conclusions: The main microorganism determined was of fungal origin associated with leukocytes, azotemia and high cellularity.

Bladder cancer in Spain 2011: population based study.

PURPOSE: We estimate the annual incidence of bladder cancer in Spain and describe the clinical profile of patients with bladder cancer enrolled in a population based study. MATERIALS AND METHODS: Using the structure of the Spanish National Health System as a basis, in 2011 the AEU (Spanish Association of Urology) conducted this study with a representative sample from 26 public hospitals and a reference population of 10,146,534 inhabitants, comprising 21.5% of the Spanish population. RESULTS: A total of 4,285 episodes of bladder cancer were diagnosed, of which 2,476 (57.8%) were new cases and 1,809 (42.2%) were cases of recurrence, representing an estimated 11,539 new diagnoses annually in Spain. The incidence of bladder cancer in Spain, age adjusted to the standard European population, was 20.08 cases per 100,000 inhabitants (95% CI 13.9, 26.3). Of patients diagnosed with a first episode of bladder cancer 84.3% were male, generally older than 59 years (81.7%) with a mean ± SD age of 70.5 ± 11.4 years. Of these patients 87.5% presented with some type of clinical symptom, with macroscopic hematuria (90.8%) being the most commonly detected. The majority of primary tumors were nonmuscle invasive (76.7%) but included a high proportion of high grade tumors (43.7%). According to the ISUP (International Society of Urologic Pathology)/WHO (2004) classification 51.1% was papillary high grade carcinoma. Carcinoma in situ was found in 2.2% of primary and 5.8% of recurrent cases. CONCLUSIONS: The incidence of bladder cancer in Spain, age adjusted to the standard European population, confirms that Spain has one of the highest incidences in Europe. Most primary nonmuscle invasive bladder cancer corresponded to high risk patients but with a low detected incidence of carcinoma in situ.

Herd-level risk factors for hock injuries in freestall-housed dairy cows in the northeastern United States and California.

The aim of this study was to investigate the associations between management and facility design factors and the prevalence of hock injuries in high-producing dairy cows in 76 freestall herds in the northeastern United States (NE-US; Vermont, New York, Pennsylvania) and California (CA). One group of high-production multiparous cows was monitored on each farm, and data on management, facility and stall design, and the conditions of the hocks were collected. Focal cows [n=38 ± 3 (mean ± standard deviation)] were evaluated for hock injuries using a 3-point scale (where 1=healthy and 3=evidently swollen or severe injury). Measures associated with the proportion (logit-transformed) of cows having injuries (score ≥ 2) or severe injuries (score=3) at the univariable level were submitted to multivariable general linear models. In NE-US, overall hock injuries increased with the percentage of stalls with fecal contamination [odds ratio (OR)=1.26; 95% confidence interval (CI)=1.02-1.54, for a 10% increase], and with the use of sawdust as bedding (OR=3.47; CI=1.14-10.62), and decreased with deep bedding (i.e., at least 10 cm depth of any type of bedding; OR=0.05; CI=0.02-0.14), use of sand as bedding (OR=0.06; CI=0.02-0.15), bedding dry matter (DM) ≥ 83.9% (OR=0.08; CI=0.03-0.20), and access to pasture during the dry period (OR=0.17; CI=0.05-0.53). When these variables were submitted to a multivariable model, the presence of deep bedding was the only factor that remained significant, explaining 54% of the variation in overall injuries. Severe hock injuries increased with the use of automatic scrapers (OR=2.29; CI=1.11-4.71) and the percentage of stalls with fecal contamination (OR=1.14; CI=1.00-1.31, for a 10% increase), and decreased with sand bedding (OR=0.22; CI=0.10-0.49), deep bedding (OR=0.24; CI=0.11-0.52), bedding DM ≥ 83.9% (OR=0.28; CI=0.14-0.58), and access to pasture during the dry period (OR=0.42; CI=0.18-0.97). The final multivariable model, which explained 36% of the variation in severe hock injuries, included the use of automatic scrapers and deep bedding. In CA, stall stocking density (OR=1.41; CI=1.00-2.01, for a 10% increase) and poor bedding maintenance (OR=1.08; CI=1.01-1.16, for a 2.5-cm decrease in depth of deep-bedded stalls) were associated with an increase of overall and severe hock injuries, respectively. Deep-bedded and well-maintained stalls reduce the risk of hock injuries. Regional variation in risk factors for these injuries should be considered when formulating on-farm recommendations.

Isolation of cholesterol- and deoxycholate-degrading bacteria from soil samples: evidence of a common pathway.

Nineteen different steroid-degrading bacteria were isolated from soil samples by using selective media containing either cholesterol or deoxycholate as sole carbon source. Strains that assimilated cholesterol (17 COL strains) were gram-positive, belonging to the genera Gordonia, Tsukamurella, and Rhodococcus, and grew on media containing other steroids but were unable to use deoxycholate as sole carbon source. Surprisingly, some of the COL strains unable to grow using deoxycholate as sole carbon source were able to catabolize other bile salts (e.g., cholate). Conversely, strains able to grow using deoxycholate as the sole carbon source (two DOC isolates) were gram-negative, belonging to the genus Pseudomonas, and were unable to catabolize cholesterol and other sterols. COL and DOC were included into the corresponding taxonomic groups based on their morphology (cells and colonies), metabolic properties (kind of substrates that support bacterial growth), and genetic sequences (16S rDNA and rpoB). Additionally, different DOC21 Tn5 insertion mutants have been obtained. These mutants have been classified into two different groups: (1) those affected in the catabolism of bile salts but that, as wild type, can grow in other steroids and (2) those unable to grow in media containing any of the steroids tested. The identification of the insertion point of Tn5 in one of the mutants belonging to the second group (DOC21 Mut1) revealed that the gene knocked-out encodes an A-ring meta-cleavage dioxygenase needed for steroid catabolism.

Herd-level risk factors for lameness in freestall farms in the northeastern United States and California.

The objective was to investigate the association between herd-level management and facility design factors and the prevalence of lameness in high-producing dairy cows in freestall herds in the northeastern United States (NE; Vermont, New York, Pennsylvania) and California (CA). Housing and management measures such as pen space, stall design, bedding type, and milking routine were collected for the high-producing pen in 40 farms in NE and 39 farms in CA. All cows in the pen were gait scored using a 1-to-5 scale and classified as clinically lame (score ≥3) or severely lame (score ≥4). Measures associated with the (logit-transformed) proportion of clinically or severely lame cows at the univariable level were submitted to multivariable general linear models. In NE, lameness increased on farms that used sawdust bedding [odds ratio (OR)=1.71; 95% confidence interval (CI)=1.06-2.76] and decreased with herd size (OR=0.94; CI=0.90-0.97, for a 100-cow increase), use of deep bedding (OR=0.48; CI=0.29-0.79), and access to pasture (OR=0.52; CI=0.32-0.85). The multivariable model included herd size, access to pasture, and provision of deep bedding, and explained 50% of the variation in clinical lameness. Severe lameness increased with the percentage of stalls with fecal contamination (OR=1.15; CI=1.06-1.25, for a 10% increase) and with use of sawdust bedding (OR=2.13; CI=1.31-3.47), and decreased with use of deep bedding (OR=0.31; CI=0.19-0.50), sand bedding (OR=0.32; CI=0.19-0.53), herd size (OR=0.93; CI=-0.89-0.97, for a 100-cow increase), and rearing replacement heifers on site (OR=0.57; CI=0.32-0.99). The multivariable model included deep bedding and herd size, and explained 59% of the variation of severe lameness. In CA, clinical lameness increased with the percentage of stalls containing fecal contamination (OR=1.15; CI=1.05-1.26, for a 10% increase), and decreased with herd size (OR=0.96; CI=0.94-0.99, for a 100-cow increase), presence of rubber in the alley to the milking parlor (OR=0.46; CI=0.28-0.76), distance of the neck rail from the rear curb (OR=0.97; CI=0.95-0.99, for a 1-cm increase), water space per cow (OR=0.92; CI=0.85-0.99, for a 1-cm increase), and increased frequency of footbaths per week (OR=0.90; CI=081-0.99, for a 1-unit increase). The multivariable model included herd size, percentage of stalls containing fecal contamination, and presence of rubber in the alley to the milking parlor, and explained 44% of the variation of clinical lameness. Severe lameness increased with the percentage of stalls containing fecal contamination (OR=1.23; CI=1.06-1.42, for a 10% increase) and decreased with frequency of manure removal in the pen per day (OR=0.72; CI=0.53-0.97, for a 1-unit increase). The final model included both variables and explained 28% of the variation in severe lameness. In conclusion, changes in housing and management may help decrease the prevalence of lameness on dairy farms, but key risk factors vary across regions.

Inertial attitude control of a bat-like morphing-wing air vehicle.

This paper presents a novel bat-like unmanned aerial vehicle inspired by the morphing-wing mechanism of bats. The goal of this paper is twofold. Firstly, a modelling framework is introduced for analysing how the robot should manoeuvre by means of changing wing morphology. This allows the definition of requirements for achieving forward and turning flight according to the kinematics of the wing modulation. Secondly, an attitude controller named backstepping+DAF is proposed. Motivated by biological evidence about the influence of wing inertia on the production of body accelerations, the attitude control law incorporates wing inertia information to produce desired roll (ϕ) and pitch (θ) acceleration commands (desired angular acceleration function (DAF)). This novel control approach is aimed at incrementing net body forces (F(net)) that generate propulsion. Simulations and wind-tunnel experimental results have shown an increase of about 23% in net body force production during the wingbeat cycle when the wings are modulated using the DAF as a part of the backstepping control law. Results also confirm accurate attitude tracking in spite of high external disturbances generated by aerodynamic loads at airspeeds up to 5 ms⁻¹.

Role of fibroblast growth factor 23 (FGF23) in the metabolism of phosphorus and calcium immediately after kidney transplantation.

INTRODUCTION: Persistence of inappropriately high serum levels of fibroblast growth factor-23 (FGF23), a recently discovered phosphaturic hormone, has been reported to play an important role in the pathogenesis of posttransplant hypophosphatemia. The aim of the present study was to evaluate FGF23 in the early posttransplant period and study the complex associations between FGF23, parathyroid hormone (PTH), 1,25(OH)(2) vitamin D, and phosphate in transplant patients. MATERIALS AND METHODS: We performed a cross-sectional observational study of 42 adult kidney recipients in the early posttransplant period (<6 months). Fasting serum samples and 24-hour urine samples were collected during a routine follow-up outpatient visit. Serum creatinine, calcium, phosphate, magnesium and urinary creatinine, calcium, magnesium, and phosphate were measured using standard assays. We also studied concentrations of 25 hydroxyvitamin D, 1,25(OH)(2) vitamin D, intact PTH, and circulating FGF23. RESULTS: Median values for the different parameters studied were as follows: 9.9 ± 0.6 mg/dL, phosphatemia 3.3 ± 0.7 mg/dL, estimated glomerular filtration rate (eGFR; 41.1 ± 14.0 mL/min, phosphate reabsorption rate 68.4% ± 10.7%, PTH 94.5 ng/L (53.8-199.5), calcitriol 33.0 pg/mL (24.0-44.1), calcidiol 27.3 ng/mL (17.0-38.0), FGF23 139 pg/mL (88-221), and calciuria 62.5 mg/d (40.3-101.3). The variables significantly associated with serum FGF23 levels were phosphate reabsorption rate (r = .493; P = .001), calcitriol (r = .399; P = .009), eGFR (r = .557; P < .001), PTH (0.349; P = .024). CONCLUSIONS: Elevated serum levels of FGF23 could explain the deficiency of calcitriol and elevated renal phosphorus wasting in the early posttransplant period. All treatments that can lead to increased serum phosphate levels (eg, oral medication or calcitriol) should be carefully evaluated, since increased phosphatemia could further stimulate secretion of FGF23 and prolong high phosphorus loss.

Benchmarking cow comfort on North American freestall dairies: lameness, leg injuries, lying time, facility design, and management for high-producing Holstein dairy cows.

In this paper, we describe a novel approach to corporate involvement in on-farm assessment, driven by the desire to provide a service for dairy producers and to create a vehicle for engagement on issues of dairy cow welfare. This program provides producers with feedback on animal-based (including gait score, leg injuries, and lying time) and facility-based (including freestall design, bedding practices, feed bunk design and management, and stocking density) measures that can be used to better address their management goals. The aim of this paper is to describe variation in the prevalence of lameness and leg injuries, lying behavior, facility design, and management practices for high-producing cows on freestall dairy farms in 3 regions of North America: British Columbia (BC; n=42); California (CA; n=39); and the northeastern United States (NE-US; n=40). Prevalence of clinical lameness averaged (mean ± SD) 27.9±14.1% in BC, 30.8±15.5% in CA, and 54.8±16.7% in NE-US; prevalence of severe lameness averaged 7.1±5.4% in BC, 3.6±4.2% in CA, and 8.2±5.6% in NE-US. Overall prevalence of hock injuries was 42.3±26.2% in BC, 56.2±21.6% in CA, and 81.2±22.5% in NE-US; prevalence of severe injuries was 3.7±5.2% in BC, 1.8±3.1% in CA, 5.4±5.9% in NE-US. Prevalence of swollen knees was minimal in CA (0.3±0.6%) but high (23.1±16.3%) in NE-US (not scored in BC). Lying times were similar across regions (11.0±0.7h/d in BC, 10.4±0.8h/d in CA, 10.6±0.9h/d in NE-US), but individual lying times among cows assessed varied (4.2 to 19.5h/d, 3.7 to 17.5h/d, and 2.8 to 20.5h/d in BC, CA, and NE-US, respectively). These results showed considerable variation in lameness and leg injury prevalence as well as facility design and management among freestall farms in North America. Each of the 3 regions had farms with a very low prevalence of lameness and injuries, suggesting great opportunities for improvement on other farms within the region.

Biomechanics of smart wings in a bat robot: morphing wings using SMA actuators.

This paper presents the design of a bat-like micro aerial vehicle with actuated morphing wings. NiTi shape memory alloys (SMAs) acting as artificial biceps and triceps muscles are used for mimicking the morphing wing mechanism of the bat flight apparatus. Our objective is twofold. Firstly, we have implemented a control architecture that allows an accurate and fast SMA actuation. This control makes use of the electrical resistance measurements of SMAs to adjust morphing wing motions. Secondly, the feasibility of using SMA actuation technology is evaluated for the application at hand. To this purpose, experiments are conducted to analyze the control performance in terms of nominal and overloaded operation modes of the SMAs. This analysis includes: (i) inertial forces regarding the stretchable wing membrane and aerodynamic loads, and (ii) uncertainties due to impact of airflow conditions over the resistance-motion relationship of SMAs. With the proposed control, morphing actuation speed can be increased up to 2.5 Hz, being sufficient to generate lift forces at a cruising speed of 5 m s(-1).

Bending continuous structures with SMAs: a novel robotic fish design.

In this paper, we describe our research on bio-inspired locomotion systems using deformable structures and smart materials, concretely shape memory alloys (SMAs). These types of materials allow us to explore the possibility of building motor-less and gear-less robots. A swimming underwater fish-like robot has been developed whose movements are generated using SMAs. These actuators are suitable for bending the continuous backbone of the fish, which in turn causes a change in the curvature of the body. This type of structural arrangement is inspired by fish red muscles, which are mainly recruited during steady swimming for the bending of a flexible but nearly incompressible structure such as the fishbone. This paper reviews the design process of these bio-inspired structures, from the motivations and physiological inspiration to the mechatronics design, control and simulations, leading to actual experimental trials and results. The focus of this work is to present the mechanisms by which standard swimming patterns can be reproduced with the proposed design. Moreover, the performance of the SMA-based actuators' control in terms of actuation speed and position accuracy is also addressed.

Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients.

UNLABELLED: BK virus (BKV) nephropathy is a common viral infection in renal transplant patients, with a prevalence of 1-9% at approximately 12 months after surgery. While it is widely agreed that reduction of immunosuppression should be the first intervention after diagnosis of BKV infection, there is no consensus on whether calcineurin inhibitors or antiproliferative drugs should be reduced first. Furthermore, target levels of immunosuppressive drugs are poorly defined, as are criteria for replacing one immunosuppressive agent with another. RESULTS: We report our series of 15 renal transplant patients who underwent surgery between September 2004 and March 2010 and who developed BKV infection. The first 8 patients were treated with reduction of immunosuppression; 7 of these patients received cidofovir and 6 received intravenous immunoglobulin. The remaining 7 renal transplant recipients received mammalian target of rapamycin inhibitors (imTOR). In this group, we observed faster and more efficacious BKV clearance in plasma and urine and a steady improvement in allograft function, with no episodes of acute allograft rejection during follow-up. The polymerase chain reaction assay for BKV in urine became positive in 2 patients in whom imTOR were stopped due to severe side effects. CONCLUSIONS: The use of imTOR should be considered a first step in the treatment of renal transplant recipients with BKV infection. In our experience, this change in treatment was safe and resulted in viral clearance.

Incidence and risk factors for the metabolic syndrome and posttransplant diabetes in renal transplant recipients taking tacrolimus.

OBJECTIVES: We investigated the incidence and risk factors for the metabolic syndrome (MS) and posttransplant diabetes mellitus (PTDM) among renal transplant recipients on tacrolimus-based immunosuppressive regimens during the first year posttransplant. In addition, we studied the relationship between MS and PTDM with transplant renal function at 1 year. METHODS: We included the 100 patients who received a renal transplant in our unit between January 2007 and June 2008, collecting demographic, clinical and biochemical characteristics at 1, 6, and 12 months posttransplantation. We excluded 15% of patients with pretransplantation diabetes. MS was defined according to the National Cholesterol Education Program criteria and PTDM according to World Health Organization criteria. Insulin resistance at one year posttransplant was measured using the homeostasis model assessment (HOMA) index. RESULTS: Insulin therapy was required in 46% of patients during the first hospitalization and hyperglycemia was present in 65% of the cases. The incidence of PTDM decreased throughout the first year posttransplant, namely, 44%, 24%, and 13% at 1, 6, and 12 months, respectively. The incidence of MS increased to 33%, 48% and 50% at 1, 6, and 12 months, respectively. Age, body mass index, plasma fasting glucose levels at 1 month posttransplant, and pretransplant fasting triglyceridemia predicted PTDM. Rejection and in-patient hyperglycemia predicted MS. PTDM and MS were closely correlated (P=.004). The HOMA index was higher among patients with MS than other subjects at 1 year posttransplant: 3.2 (1.2) versus 2.3 (0.9; P=.035). Neither PTDM nor MS was associated with impaired plasma creatinine levels at 1 year after kidney transplantation. CONCLUSION: There was an high incidence of PTDM and MS among kidney transplant recipients treated with tacrolimus as the main immunosuppressive agent. The HOMA index was a good test of insulin resistance in this population. Screening and treatment of risk factors may avoid the development of these entities, which are related to poor cardiovascular outcomes.