A participatory and comprehensive intervention to improve violence prevention in two high-risk occupations: effect and process evaluation of a stepped wedge cluster randomised trial.

BACKGROUND: Work-related violence committed by clients, patients, and customers represents a major occupational health risk for employees that needs to be reduced. METHODS: We tested a comprehensive violence prevention intervention involving active participation of both employees and managers in the Prison and Probation Service (PPS) and on psychiatric wards in Denmark. We used a stepped wedge cluster randomised controlled trial design. We measured the degree of implementation of the intervention by registration of fidelity, reach, and dose and used a mixed-effects regression analysis to estimate the effects of the intervention. RESULTS: We recruited 16 work units for the intervention, but three work units dropped out. The average implementation rate was 73%. In the psychiatric wards, the intervention led to statistically significant improvements in the primary outcome (an increase in the degree to which managers and employees continuously work on violence prevention practices based on their registration and experiences), but none statistically significant improvements in any of the secondary outcomes. In the PPS units, the intervention did not lead to a statistically significant improvement in the primary outcome, but to statistically significant improvements in three secondary outcomes. CONCLUSION: Most work units were able to carry out the intervention as planned. The intervention showed mixed results regarding the primary outcome. Nevertheless, the results indicate improvements also in the sector where a change in the primary outcome was not achieved. The results point at that a participatory and comprehensive approach could be a viable way of working with violence prevention in high-risk workplaces. TRIAL REGISTRATION: ISRCTN86993466: 20/12/2017.

Development and validation of a minimally invasive and image-guided tape stripping method to sample atopic skin in children.

BACKGROUND: Molecular skin profiling techniques, typically performed on skin samples taken by punch biopsy, have enhanced the understanding of the pathophysiology of atopic dermatitis (AD), thereby enabling the development of novel targeted therapeutics. However, punch biopsies are not always feasible or desirable, and novel minimally invasive methods such as skin tape stripping have been developed. AIM: To develop, optimize and validate a novel tape stripping method guided by noninvasive in vivo skin imaging to sample atopic skin in children. METHODS: Skin tape stripping-based procedures were compared and optimized using data from 30 healthy controls (HCs: 5 adults, 25 children) and 39 atopic children. Evaluations were guided by high-resolution photography, reflectance confocal microscopy, optical coherence tomography and transepidermal water loss measurements. We assessed and compared adverse events (AEs), the time needed to perform the sampling and the cDNA levels obtained from the tapes. RESULTS: Tape stripping methods based on previously described protocols resulted in erosions in all participants and required a median time of 65 min to perform (range 60-70 min), but provided good cDNA yield. Shorter durations appeared less invasive but provided lower cDNA yield. The final optimized tape stripping protocol, using 11 tapes of 22 mm in diameter, each applied twice for 5 s with 90° rotation, did not produce significant AEs, was completed within a median time of 7 min (range 5-15 min) and provided good cDNA yield both in HCs and atopic children. CONCLUSION: Our minimally invasive method is safe and reliable, and provides reproducible acquisition of cDNA in atopic children. In addition, it enables rapid sample collection, a crucial factor in clinical practice.

Monocyte secretory profiling in a clinical and MEFV genotype-characterized cohort of Danish familial Mediterranean fever patients: diagnostic potential of CCL1 and CXCL1.

OBJECTIVE: The autoinflammatory disease familial Mediterranean fever (FMF), characterized by recurrent attacks of sterile fever, serosal, and/or synovial inflammation, is caused by variants in the Mediterranean fever gene, MEFV, coding for the pyrin inflammasome sensor. The diagnosis of FMF is mainly based on clinical symptoms and confirmed by detection of disease-associated MEFV variants. However, the diagnosis is challenging among patients carrying variants of uncertain clinical significance (VUS). In this study, we aimed to identify potential FMF discriminatory diagnostic markers in a cohort of clinically characterized FMF patients. METHOD: We established a cohort of clinically and MEFV genotype-characterized FMF patients by enrolling patients from major Danish hospitals (n = 91). The secretory profile of pyrin inflammasome-activated monocytes from healthy donors (HDs) and MEFV-characterized FMF patients (n = 28) was assessed by analysing cell supernatants for a custom-designed panel of 23 cytokines, chemokines, and soluble tumour necrosis factor receptors associated with monocyte and macrophage function. RESULTS: MEFV genotypes in Danish FMF patients were associated with age at symptom onset (p < 0.05), FMF among relatives (p < 0.01), proportion of patients in colchicine treatment (p < 0.01), and treatment response (p < 0.05). Secretion of chemokines CCL1 and CXCL1 from pyrin-activated FMF monocytes was significantly decreased compared to HDs (p < 0.05), and could discriminate FMF patients with 'non-confirmatory' MEFV genotypes from HDs with 80.0% and 70.0% sensitivity for CCL1 and CXCL1, respectively (p < 0.05). CONCLUSION: Our data suggest that a functional diagnostic assay based on CCL1 or CXCL1 levels in pyrin-activated patient monocytes may contribute to FMF diagnosis in patients with VUS.

A Dilp8-dependent time window ensures tissue size adjustment in Drosophila.

The control of organ size mainly relies on precise autonomous growth programs. However, organ development is subject to random variations, called developmental noise, best revealed by the fluctuating asymmetry observed between bilateral organs. The developmental mechanisms ensuring bilateral symmetry in organ size are mostly unknown. In Drosophila, null mutations for the relaxin-like hormone Dilp8 increase wing fluctuating asymmetry, suggesting that Dilp8 plays a role in buffering developmental noise. Here we show that size adjustment of the wing primordia involves a peak of dilp8 expression that takes place sharply at the end of juvenile growth. Wing size adjustment relies on a cross-organ communication involving the epidermis as the source of Dilp8. We identify ecdysone signaling as both the trigger for epidermal dilp8 expression and its downstream target in the wing primordia, thereby establishing reciprocal hormonal feedback as a systemic mechanism, which controls organ size and bilateral symmetry in a narrow developmental time window.

Swine diets: Impact of carbohydrate sources on manure characteristics and gas emissions.

Swine growers seeking to lower costs and environmental impact have turned to alternative carbohydrate feed sources. A feeding trial was conducted to determine the effect carbohydrate sources have on manure composition and gas emissions. A total of 48 gilts averaging 138 kg BW were fed diets consisting of (a) low fiber (LF) grain, or (b) high fiber (HF) aro-industrial co-product (AICP). The LF diets included corn and soybean meal (CSBM) and barley soybean meal (BSBM). The HF AICP diets were CSBM based and supplemented with one of the following materials: beet pulp; corn distillers dried grains with solubles; soybean hulls; or wheat bran. Diets were fed for 42 d with an average daily feed intake of 2.71 kg d-1. Feces and urine were collected twice daily and added to manure storage containers in which manure slurries were monitored for gas emissions and chemical properties. Manures of animals fed HF diets had significantly (P < 0.05) more excretion of solids, C, N, and organic N, but less total S compared to pigs fed the LF diets. Animals feed HF diets had significantly (P < 0.05) higher levels of ammonia, sulfide, volatile fatty acids, and phenols in manure compared to pigs fed the LF diets. Manure of animals fed HF diets had 30% (P < 0.05) lower NH3 and 17% lower hydrogen sulfide emissions; however, fiber had no impact on odor emissions. Based on the partitioning of nutrients, animals fed HF fiber diets had increased manure retention for C and N but decreased levels of N gas emissions and manure S. There were little differences in manure and gas emissions for animals fed LF diets, but the source of HF AICP diets had a significant impact on manure composition and gas emissions.

Swine diets impact manure characteristics and gas emissions: Part II protein source.

Soybean meal is the dominate protein source for swine diets in the world driven largely by economics, nutritive value, and availability; but conditions can change requiring growers to consider more economical and available protein alternatives. A feeding trial was conducted to determine the impact dietary protein source material on manure slurry chemical properties and manure gas emissions. A total of 32 gilts averaging 130 kg BW were fed either a control diet formulated with soybean meal (SB) or an alternative protein source that included corn gluten meal (CG); canola meal (CM); or poultry meal (PM), with all diets containing 176 g protein kg-1. Diets were fed for 45 d with an average daily feed intake of 2.68 kg/d. Feces and urine were collected twice daily after each feeding and added to animal-specific manure storage containers. At the end of the study, manure slurries were monitored for gas emissions and chemical properties. Dietary protein source had a significant effect (P < 0.05) on manure pH, total solids, total C, protein N, and total S. Pigs fed the diets containing CM had significantly higher levels of sulfide, butanoic acid, and branch chain fatty acids compared to pigs fed SB diets (P < 0.05). Pigs fed CM diets had significantly lower emissions of NH3 compared to pigs fed SB diets (P < 0.05). There were no significant differences in C or S emissions or in odorant emission as affected by source of dietary protein. Hydrogen sulfide was the most dominate odorants for all dietary treatments.

Swine diets impact manure characteristics and gas emissions: Part I protein level.

Crude protein (CP) is a key nutrient in swine diets supplying essential amino acids, N, and S to animals for growth are fed in excess to maximize growth. Swine diets reduced in CP and supplemented with crystalline amino acids have been shown effective at maintaining animal growth while increasing overall CP use efficiency. A feeding trial study was conducted to determine the effects of reduced dietary CP levels on manure slurry chemical properties and gas emissions. A total of 24 gilts averaging 111 kg BW were fed corn and soybean meal diets formulated with 8.7, 14.8, and 17.6% CP using crystalline amino acid supplementation in the 8.7 and 14.8% CP diets, but only intact protein, soybean meal, in the diet containing 17.6% CP. Diets were fed for 45 d with an average daily feed intake (ADFI) of 2.70 kg across all diets. Animals were fed twice daily with both feces and urine collected during each feeding and added to animal-specific manure storage containers. At the end of the study, manure slurries were monitored for gas emissions and chemical properties. Increasing dietary CP levels increased manure pH, total solids, total N, and total S, including increased levels of ammonia (NH3), volatile fatty acids, and phenolic compounds. Pigs fed lower CP diets had lower emissions of NH3, branched chain fatty acids (BCFA), and phenol compounds which translated into lower emissions in total odor. Emissions of NH3 and odor were reduced by 8.9% and 4.2%, respectively, for each unit percent decline in dietary CP. Hydrogen sulfide was the dominate odorant associated with manure odor emissions. Based on nutrient mass balance, animal retention of dietary N and S increased by 7.0% and 2.4%, respectively, for each unit percent drop in crude protein fed animals, while C retention in the animal declined by 2.1%.

Characteristics of patients with familial Mediterranean fever in Denmark: a retrospective nationwide register-based cohort study.

Objectives: To investigate epidemiology, demography, and genetic and clinical characteristics of patients with familial Mediterranean fever (FMF) in Denmark. Method: In this population-based, cross-sectional cohort study, we identified FMF patients from discharge diagnoses using ICD-10 codes in the Danish National Patient Register, and linked data from the Danish Civil Registration System and laboratory databases for results of MEFV gene variant screening. Results: We identified 495 FMF patients (prevalence 1:11 680) with a median age of 29 years and a female ratio of 51%. The median age at diagnosis of FMF was 13 (IQR 7-22) years, with an estimated median diagnostic delay of 3 (IQR 0.7-6.9) years. The predominant ethnicities were Turkish (41.8%), Lebanese (15.8%), Syrian (6.5%), South-West Asian (7.9%), and South-East Asian (3.0%). The MEFV genotype distribution was 18.7% homozygous, 21.2% compound heterozygous, 32.0% heterozygous, 11.0% with complex alleles or unresolved zygosity, and 17.1% with no detected variants. M694V was the most prevalent variant in the overall cohort (32.5%). Homozygous or compound heterozygous MEFV exon 10 variants were associated with younger age at diagnosis (p < 0.001) and reduced number of hospital contacts before diagnosis (p = 0.008). The Charlson Comorbidity Index was ≥ 2 in 8.1% of patients. The prevalence of amyloidosis was 1.0%. Conclusions: FMF in Denmark is rare and patients are mainly of Eastern Mediterranean ethnicity. Diagnostic delay was long but patients with exon 10 MEFV variants were diagnosed at a younger age. Prolonged diagnostic delay is probably caused by lack of FMF awareness in the Danish healthcare system.

Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared late complication. Treatment options are lacking at present. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with adipose-derived regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up. MATERIAL AND METHODS: We included 10 patients with BCRL. ADRCs were injected directly into the axillary region together with a scar-releasing fat grafting procedure. Primary endpoint was change in arm volume. Secondary endpoints were change in patient-reported outcomes, changes in lymph flow, and safety. RESULTS: During follow-up, no significant change in volume was noted. Patient-reported outcomes improved significantly with time. Five patients reduced their use of conservative management. Quantitative lymphoscintigraphy did not improve on the lymphedema-affected arms. ADRCs were well tolerated, and only minor transient adverse events related to liposuction were noted. CONCLUSIONS: In this pilot study, a single injection of ADRCs improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events during the follow-up period. Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There was no change in excess arm volume. Results of this trial need to be confirmed in randomized clinical trials.

Narasin effects on energy, nutrient, and fiber digestibility in corn-soybean meal or corn-soybean meal-dried distillers grains with solubles diets fed to 16-, 92-, and 141-kg pigs.

Three experiments were conducted to determine the effect of narasin on growth performance and on GE and nutrient digestibility in nursery, grower, and finishing pigs fed either a corn-soybean meal (CSBM) diet or a CSBM diet supplemented with distillers dried grains with solubles (DDGS), in combination with either 0 or 30 mg narasin/kg of diet. In Exp. 1 (64 gilts, initial BW = 9.0 kg, SD = 1.0 kg) and Exp. 2 (60 gilts. initial BW = 81.1 kg, SD = 6.1 kg), gilts were allotted into individual pens and fed their experimental diets for 24 and 21 d, respectively. On the last 2 d of each experiment, fecal samples were collected to assess apparent total tract digestibility (ATTD) of GE and various nutrients. In Exp. 3, 2 separate groups of 24 gilts (initial BW = 145.1 kg, SD = 7.8 kg) were allotted to individual metabolism crates and fed their experimental diets for 30 d prior to a time-based 6-d total fecal collection period to assess GE and nutrient digestibility. In Exp. 1, there was an interaction between diet type and narasin addition for G:F and for many of the ATTD coefficients measured. When narasin was supplemented to the CSBM diet, ATTD of GE, DM, C, S, phosphorus, NDF, and ADF was either not changed or reduced, while when narasin was supplemented to DDGS diets, these same ATTD parameters were increased (interaction, ≤ 0.05). Even though ADG and ADFI were not affected, G:F was improved in pigs fed the CSBM diet with supplemental narasin, but was reduced in pigs fed the DDGS diet with supplemental narasin (interaction, < 0.05). In Exp. 2, there was an interaction between diet type and narasin supplementation only for ATTD of Ca (interaction, < 0.01), in that narasin supplementation did not change the ATTD of Ca in pigs fed the CSBM diet, while narasin supplementation reduced the ATTD of Ca in pigs fed the DDGS containing diet. In Exp. 3, there was an interaction between diet and narasin only for ATTD of C (interaction, < 0.01) in that narasin supplementation resulted in an increased ATTD of C in pigs fed the CSBM diet, while narasin supplementation to the DDGS containing diet resulted in a reduced ATTD of Ca. In general, the data indicate that narasin interacted with and had its largest effect on pig performance and GE or nutrient digestibility in 9 to 23 kg pigs compared to pigs weighing greater than 80 kg. The data also indicate that the addition of DDGS reduced GE, DM, Ca, and N digestibility, regardless of BW.

Growth of elaborate microbial pinnacles in Lake Vanda, Antarctica.

Microbial pinnacles in ice-covered Lake Vanda, McMurdo Dry Valleys, Antarctica, extend from the base of the ice to more than 50 m water depth. The distribution of microbial communities, their photosynthetic potential, and pinnacle morphology affects the local accumulation of biomass, which in turn shapes pinnacle morphology. This feedback, plus environmental stability, promotes the growth of elaborate microbial structures. In Lake Vanda, all mats sampled from greater than 10 m water depth contained pinnacles with a gradation in size from <1-mm-tall tufts to pinnacles that were centimeters tall. Small pinnacles were cuspate, whereas larger ones had variable morphology. The largest pinnacles were up to ~30 cm tall and had cylindrical bases and cuspate tops. Pinnacle biomass was dominated by cyanobacteria from the morphological and genomic groups Leptolyngbya, Phormidium, and Tychonema. The photosynthetic potential of these cyanobacterial communities was high to depths of several millimeters into the mat based on PAM fluorometry, and sufficient light for photosynthesis penetrated ~5 mm into pinnacles. The distribution of photosynthetic potential and its correlation to pinnacle morphology suggests a working model for pinnacle growth. First, small tufts initiate from random irregularities in prostrate mat. Some tufts grow into pinnacles over the course of ~3 years. As pinnacles increase in size and age, their interiors become colonized by a more diverse community of cyanobacteria with high photosynthetic potential. Biomass accumulation within this subsurface community causes pinnacles to swell, expanding laminae thickness and creating distinctive cylindrical bases and cuspate tops. This change in shape suggests that pinnacle morphology emerges from a specific distribution of biomass accumulation that depends on multiple microbial communities fixing carbon in different parts of pinnacles. Similarly, complex patterns of biomass accumulation may be reflected in the morphology of elaborate ancient stromatolites.

Impact of fiber source and feed particle size on swine manure properties related to spontaneous foam formation during anaerobic decomposition.

Foam accumulation in deep-pit manure storage facilities is of concern for swine producers because of the logistical and safety-related problems it creates. A feeding trial was performed to evaluate the impact of feed grind size, fiber source, and manure inoculation on foaming characteristics. Animals were fed: (1) C-SBM (corn-soybean meal): (2) C-DDGS (corn-dried distiller grains with solubles); and (3) C-Soybean Hull (corn-soybean meal with soybean hulls) with each diet ground to either fine (374 µm) or coarse (631 µm) particle size. Two sets of 24 pigs were fed and their manure collected. Factors that decreased feed digestibility (larger grind size and increased fiber content) resulted in increased solids loading to the manure, greater foaming characteristics, more particles in the critical particle size range (2-25 µm), and a greater biological activity/potential.

Lab-assay for estimating methane emissions from deep-pit swine manure storages.

Methane emission is an important tool in the evaluation of manure management systems due to the potential impact it has on global climate change. Field procedures used for estimating methane emission rates require expensive equipment, are time consuming, and highly variable between farms. The purpose of this paper is to report a simple laboratory procedure for estimating methane emission from stored manure. The test developed was termed a methane production rate (MPR) assay as it provides a short-term biogas production measurement. The MPR assay incubation time is short (3d), requires no sample preparation in terms of inoculation or dilution of manure, is incubated at room temperature, and the manure is kept stationary. These conditions allow for high throughput of samples and were chosen to replicate the conditions within deep-pit manure storages. In brief, an unaltered aliquot of manure was incubated at room temperature for a three-days to assay the current rate of methane being generated by the manure. The results from this assay predict an average methane emission factor of 12.2 ± 8.1 kg CH4 head(-1) yr(-1) per year, or about 5.5 ± 3.7 kg CH4 per finished animal, both of which compare well to literature values of 5.5 ± 1.1 kg CH4 per finished pig for deep-pit systems (Liu et al., 2013). The average methane flux across all sites and months was estimated to be 22 ± 17 mg CH4 m(-2)-min(-1), which is within literature values for deep-pit systems ranging from 0.24 to 63 mg CH4 m(-2)-min(-1) (Park et al., 2006) and similar to the 15 mg CH4 m(-2)-min(-1) estimated by (Zahn et al., 2001).

Growth of modern branched columnar stromatolites in Lake Joyce, Antarctica.

Modern decimeter-scale columnar stromatolites from Lake Joyce, Antarctica, show a change in branching pattern during a period of lake level rise. Branching patterns correspond to a change in cyanobacterial community composition as preserved in authigenic calcite crystals. The transition in stromatolite morphology is preserved by mineralized layers that contain microfossils and cylindrical molds of cyanobacterial filaments. The molds are composed of two populations with different diameters. Large diameter molds (>2.8 µm) are abundant in calcite forming the oldest stromatolite layers, but are absent from younger layers. In contrast, <2.3 µm diameter molds are common in all stromatolites layers. Loss of large diameter molds corresponds to the transition from smooth-sided stromatolitic columns to branched and irregular columns. Mold diameters are similar to trichome diameters of the four most abundant living cyanobacteria morphotypes in Lake Joyce: Phormidium autumnale morphotypes have trichome diameters >3.5 µm, whereas Leptolyngbya antarctica, L. fragilis, and Pseudanabaena frigida morphotypes have diameters <2.3 µm. P. autumnale morphotypes were only common in mats at <12 m depth. Mats containing abundant P. autumnale morphotypes were smooth, whereas mats with few P. autumnale morphotypes contained small peaks and protruding bundles of filaments, suggesting that the absence of P. autumnale morphotypes allowed small-scale topography to develop on mats. Comparisons of living filaments and mold diameters suggest that P. autumnale morphotypes were present early in stromatolite growth, but disappeared from the community through time. We hypothesize that the mat-smoothing behavior of P. autumnale morphotypes inhibited nucleation of stromatolite branches. When P. autumnale morphotypes were excluded from the community, potentially reflecting a rise in lake level, short-wavelength roughness provided nuclei for stromatolite branches. This growth history provides a conceptual model for initiation of branched stromatolite growth resulting from a change in microbial community composition.

Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells.

Obesity and type 2 diabetes lead to dramatically increased risks of atherosclerosis and CHD. Multiple mechanisms converge to promote atherosclerosis by increasing endothelial oxidative stress and up-regulating expression of pro-inflammatory molecules. Microvesicles (MV) are small ( < 1 µm) circulating particles that transport proteins and genetic material, through which they are able to mediate cell-cell communication and influence gene expression. Since MV are increased in plasma of obese, insulin-resistant and diabetic individuals, who often exhibit chronic vascular inflammation, and long-term feeding of a high-fat diet (HFD) to rats is a well-described model of obesity and insulin resistance, we hypothesised that this may be a useful model to study the impact of MV on endothelial inflammation. The number and cellular origin of MV from HFD-fed obese rats were characterised by flow cytometry. Total MV were significantly increased after feeding HFD compared to feeding chow (P< 0·001), with significantly elevated numbers of MV derived from leucocyte, endothelial and platelet compartments (P< 0·01 for each cell type). MV were isolated from plasma and their ability to induce reactive oxygen species (ROS) formation and vascular cell adhesion molecule (VCAM)-1 expression was measured in primary rat cardiac endothelial cells in vitro. MV from HFD-fed rats induced significant ROS (P< 0·001) and VCAM-1 expression (P= 0·0275), indicative of a pro-inflammatory MV phenotype in this model of obesity. These findings confirm that this is a useful model to further study the mechanisms by which diet can influence MV release and subsequent effects on cardio-metabolic health.

[Prokaryotic community of subglacial bottom sediments of Antarctic Lake Untersee: detection by cultural and direct microscopic techniques].

The heterotrophic mesophilic component was studied in microbial communities of the samples of frozen regolith collected from the glacier near Lake Untersee collected in 2011 during the joint Russian-American expedition to central Dronning Maud Land (Eastern Antarctica). Cultural techniques revealed high bacterial numbers in the samples. For enumeration of viable cells, the most probable numbers (MPN) method proved more efficient than plating on agar media. Fluorescent in situ hybridization with the relevant oligonucleotide probes revealed members of the groups Eubacteria (Actinobacteria, Firmicutes) and Archaea. Application of the methods of cell resuscitation, such as the use of diluted media and prevention of oxidative stress, did not result in a significant increase in the numbers of viable cells retrieved form subglacial sediment samples. Our previous investigations demonstrated the necessity for special procedures for efficient reactivation of the cells from microbial communities of preserved fossil soil and permafrost samples collected in the Arctic zone. The differences in response to the special resuscitation procedures may reflect the differences in the physiological and morphological state of bacterial cells in microbial communities subject to continuous or periodic low temperatures and dehydration.

Static and predictive tomographic reconstruction for wide-field multi-object adaptive optics systems.

Multi-object adaptive optics (MOAO) systems are still in their infancy: their complex optical designs for tomographic, wide-field wavefront sensing, coupled with open-loop (OL) correction, make their calibration a challenge. The correction of a discrete number of specific directions in the field allows for streamlined application of a general class of spatio-angular algorithms, initially proposed in Whiteley et al. [J. Opt. Soc. Am. A15, 2097 (1998)], which is compatible with partial on-line calibration. The recent Learn & Apply algorithm from Vidal et al. [J. Opt. Soc. Am. A27, A253 (2010)] can then be reinterpreted in a broader framework of tomographic algorithms and is shown to be a special case that exploits the particulars of OL and aperture-plane phase conjugation. An extension to embed a temporal prediction step to tackle sky-coverage limitations is discussed. The trade-off between lengthening the camera integration period, therefore increasing system lag error, and the resulting improvement in SNR can be shifted to higher guide-star magnitudes by introducing temporal prediction. The derivation of the optimal predictor and a comparison to suboptimal autoregressive models is provided using temporal structure functions. It is shown using end-to-end simulations of Raven, the MOAO science, and technology demonstrator for the 8 m Subaru telescope that prediction allows by itself the use of 1-magnitude-fainter guide stars.

Local overexpression of the myostatin propeptide increases glucose transporter expression and enhances skeletal muscle glucose disposal.

Insulin resistance (IR) in skeletal muscle is a prerequisite for type 2 diabetes and is often associated with obesity. IR also develops alongside muscle atrophy in older individuals in sarcopenic obesity. The molecular defects that underpin this syndrome are not well characterized, and there is no licensed treatment. Deletion of the transforming growth factor-ß family member myostatin, or sequestration of the active peptide by overexpression of the myostatin propeptide/latency-associated peptide (ProMyo) results in both muscle hypertrophy and reduced obesity and IR. We aimed to establish whether local myostatin inhibition would have a paracrine/autocrine effect to enhance glucose disposal beyond that simply generated by increased muscle mass, and the mechanisms involved. We directly injected adeno-associated virus expressing ProMyo in right tibialis cranialis/extensor digitorum longus muscles of rats and saline in left muscles and compared the effects after 17 days. Both test muscles were increased in size (by 7 and 11%) and showed increased radiolabeled 2-deoxyglucose uptake (26 and 47%) and glycogen storage (28 and 41%) per unit mass during an intraperitoneal glucose tolerance test. This was likely mediated through increased membrane protein levels of GLUT1 (19% higher) and GLUT4 (63% higher). Interestingly, phosphorylation of phosphoinositol 3-kinase signaling intermediates and AMP-activated kinase was slightly decreased, possibly because of reduced expression of insulin-like growth factor-I in these muscles. Thus, myostatin inhibition has direct effects to enhance glucose disposal in muscle beyond that expected of hypertrophy alone, and this approach may offer potential for the therapy of IR syndromes.

Coordination of organ growth: principles and outstanding questions from the world of insects.

In animal species undergoing determinate growth, the making of a full-size adult body requires a series of coordinated growth events culminating in the cessation of growth that precedes sexual maturation. The merger between physiology and genetics now coming to pass in the Drosophila model allows us to decipher these growth events with an unsurpassed level of sophistication. Here, we review several coordination mechanisms that represent fundamental aspects of growth control: adaptation of growth to environmental cues, interorgan coordination, and the coordination of growth with developmental transitions. The view is emerging of an integrated process where organ-autonomous growth is coordinated with both developmental and environmental cues to define final body size.