Effects of abomasal infusion of soybean or sunflower phospholipids on nutrient digestibility and milk production in lactating dairy cows.

The fatty acid (FA) and phospholipid composition of dietary lecithin may influence FA digestibility and milk production in cattle. Eight multiparous Holstein cows (99.4 ± 9.2 d in milk [DIM]; 48.9 ± 3.8 kg milk/d) were enrolled in a 3 × 3 incomplete Latin square design with 3 treatments provided as continuous abomasal infusates spanning 14-d experimental periods: water (CON), soybean phospholipids (SOY; 74.5 g of deoiled soy lecithin), or sunflower phospholipids (SUN; 133.5 g of hydrolyzed sunflower lecithin). Cows were fed the same diet, which contained (% dry matter) 27.0% neutral detergent fiber (NDF), 15.6% crude protein (CP), 26.2% starch, and 5.87% FA. Treatments did not modify body weight, milk fat, protein, or lactose contents, or the efficiency of producing energy-corrected milk. Cows infused with SUN had greater milk yields than those receiving SOY or CON treatments. Cows infused with SUN had higher total solids, protein, and lactose yields than cows receiving the SOY or CON treatments. Sunflower phospholipids enhanced feed efficiency (milk yield/dry matter intake) relative to SOY or CON. Treatment did not affect intakes or apparent total-tract digestibilities for NDF, CP, starch, or 16-carbon (16C) FA. Cows receiving SUN had greater total FA and 18-carbon (18C) FA intakes than SOY or CON, but treatments did not impact their digestibility. Milk FA composition was modified by treatment. Cows receiving SUN had a greater concentration of polyunsaturated FA and lower concentrations of saturated FA and monounsaturated FA in milk relative to SOY or CON. In conclusion, the abomasal infusion of SUN improved milk production and milk FA composition, indicating potential benefits for dairy cow nutrition and milk quality.

Carbohydrate Ingestion Increases Interstitial Glucose and Mitigates Neuromuscular Fatigue During Single-Leg Knee Extensions.

INTRODUCTION: We aimed to investigate the neuromuscular contributions to enhanced fatigue resistance with carbohydrate ingestion, and to identify whether fatigue is associated with changes in interstitial glucose levels assessed using a continuous glucose monitor (CGM). METHODS: Twelve healthy participants (6 males, 6 females) performed isokinetic single-leg knee extensions (90°/s) at 20% of the maximal voluntary contraction (MVC) torque until MVC torque reached 60% of its initial value (i.e, task failure). Central and peripheral fatigue were evaluated every 15 min during the fatigue task using the interpolated twitch technique (ITT), and electrically evoked torque. Using a single-blinded cross-over design, participants ingested carbohydrates (CHO) (85 g sucrose/h), or a placebo (PLA), at regular intervals during the fatigue task. Minute-by-minute interstitial glucose levels measured via CGM, and whole blood glucose readings were obtained intermittently during the fatiguing task. RESULTS: CHO ingestion increased time to task failure over PLA (113 ± 69 vs. 81 ± 49 min; mean ± SD; p < 0.001) and was associated with higher glycemia as measured by CGM (106 ± 18 vs 88 ± 10 mg/dL, p < 0.001) and whole blood glucose sampling (104 ± 17 vs 89 ± 10 mg/dL, p < 0.001). When assessing the values in the CHO condition at a similar timepoint to those at task failure in the PLA condition (i.e., ~81 min), MVC torque, % voluntary activation, and 10 Hz torque were all better preserved in the CHO vs. PLA condition (p < 0.05). CONCLUSIONS: Exogenous CHO intake mitigates neuromuscular fatigue at both the central and peripheral levels by raising glucose concentrations rather than by preventing hypoglycemia.

Replacing conventional concentrates with sprouted barley or wheat: Effects on lactational performance, nutrient digestibility, and milk fatty acid profile in dairy cows.

Finite natural resources, rising human population, and climate change pose challenges to traditional crop production. Hydroponically grown fodder (i.e., sprouted grains) can be an alternative feed source for dairy cows; however, only sprouted barley has been investigated in low-producing cows. We aimed to evaluate the impact of replacing conventional concentrates with sprouted barley or wheat, grown using hydroponics, on milk production, nutrient digestibility, and milk fatty acid profile in high-producing cows. Twenty-four multiparous Holstein cows [3.25 ± 1.33 lactations; 102 ± 23 d in milk (DIM); 49 ± 4 kg/d of milk] were used in a replicated 3 × 3 Latin square design with 21-d experimental periods. Following a 2-wk covariate period, cows were fed 1 of 3 experimental diets: a total mixed ration (1) without sprouted grains (Control), or with (2) 10% sprouted barley (Barley) or (3) 10% sprouted wheat (Wheat) on a dry matter (DM) basis. Experimental diets were formulated to be isoenergetic and isonitrogenous with sprouted grains that replaced ground corn, soybean meal, canola meal, and dextrose. Sprouted grains were grown using a semi-automatic hydroponic system and harvested after 6 d of growth. Data and sample collection occurred during the last 3 d of the covariate and experimental periods. Wide ranges were observed for the DM percent of sprouted grains (12.1 to 22.9% and 13.3 to 25.7% for barley and wheat, respectively) and the ratio of sprouted fodder to seed (0.67 to 1.07 for both barley and wheat). Feeding sprouted grains did not modify yields of milk or energy-corrected milk (ECM); however, dry matter intakes (DMI) were lower for Barley, relative to Control. Feed efficiencies were greater for Barley than for Control (1.49 ± 0.03 vs. 1.43 ± 0.03 for milk yield/DMI; 1.85 ± 0.03 vs. 1.73 ± 0.04 for ECM/DMI). Yields and concentrations of milk components (i.e., fat, true protein, and lactose) were not impacted by treatment. Milk urea-N concentrations were greater for Wheat, relative to Control or Barley. Body weight (BW; 752 ± 3 vs. 742 ± 3 kg) and BW gain (6.53 ± 2.99 vs. -9.33 ± 2.91 kg/21 d) were higher for Wheat than for Control. Apparent total-tract digestibility of organic matter was greater for Wheat, relative to Barley. Digestibilities of neutral detergent fiber and starch were higher for Wheat and Control, relative to Barley, and crude protein digestibility was greater for Wheat, relative to Barley and Control. Rumination and physical activity were not impacted by treatment. In summary, replacing traditional concentrates with sprouted grains grown using hydroponics improved milk production efficiency (barley sprouts) or enhanced body weight gain (wheat sprouts). A life cycle assessment needs to be conducted to determine the net impact of this feeding strategy for the dairy industry.

Sleep quality and the intention to modify sleep behaviors among night-shift nurses.

PURPOSE: To explore the relationship between sleep quality and intent to change sleep behaviors among night-shift nurses. METHODS: Full-time night-shift nurses in a hospital setting completed a cross-sectional online survey including demographics, Snoring, Tiredness during daytime, Observed apnea, and High Blood Pressure (STOP) Questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Intention to Change Behavior Scale (ICBS). The relationship between PSQI and ICBS scores was tested using Spearman's rho correlation coefficient. RESULTS: Most participants reported poor sleep and did not engage in health behaviors that promote good sleep. There was a weak, positive relationship between PSQI and ICBS scores. Those who reported poor sleep quality indicated a high intent to improve sleep. CONCLUSION: These findings support the need for night-shift nurses to prioritize enhancing their sleep quality by advocating for policy and practice improvements. The findings also highlight the importance of support from nurse leaders, educators, and researchers to raise awareness and implement holistic strategies for better sleep health.

Presence of Spodoptera frugiperda Multiple Nucleopolyhedrovirus (SfMNPV) Occlusion Bodies in Maize Field Soils of Mesoamerica.

The occlusion bodies (OBs) of lepidopteran nucleopolyhedroviruses can persist in soil for extended periods before being transported back on to the foliage for transmission to the host insect. A sensitive insect bioassay technique was used to detect OBs of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) in 186 soil samples collected from maize fields in the southern Mexican states of Chiapas, Tabasco, Campeche, Yucatán, and Quintana Roo, as well Belize and Guatemala. Overall, 35 (18.8%) samples proved positive for SfMNPV OBs. The frequency of OB-positive samples varied significantly among Mexican states and countries (p < 0.05). Between 1.7 and 4.4% of S. frugiperda larvae that consumed OB-positive samples died from polyhedrosis disease. Restriction endonuclease analysis using PstI and HindIII confirmed that the soil-derived isolates were strains of SfMNPV and that genetic diversity was evident among the isolates. The prevalence of OB-positive soil samples did not differ with altitude or extension (area) of the maize field, but it was significantly higher in fields with the presence of living maize plants compared to those containing dead plants or crop residues (p < 0.05). Georeferenced soil samples were used to identify soil types on digitized soil maps. Lithosol and Luvisol soils had a higher than average prevalence of OB-positive samples (42−45% positive) (p = 0.006), as did Andosol, Gleysol, and Vertisol soils (33−60% OB-positive), although the sample sizes were small (<5 samples) for the latter three soils. In contrast, Cambisol soils had a lower than average prevalence of OB-positive samples (5% positive). Bioassays on Acrisol, Fluvisol, Phaeozem, and Rendzina soils resulted in intermediate levels of OB-positive samples. We conclude that certain soil types may favor OB persistence and virus-mediated biological pest control. The soil is also likely to provide a valuable source of genetic diversity for the design of virus-based insecticides against this pest.

The Oomycete Microbe-Associated Molecular Pattern, Arachidonic Acid, and an Ascophyllum nodosum-Derived Plant Biostimulant Induce Defense Metabolome Remodeling in Tomato.

Arachidonic acid (AA) is an oomycete-derived microbe-associated molecular pattern (MAMP) capable of eliciting robust defense responses and inducing resistance in plants. Similarly, Ascophylum nodosum extract (ANE) from the brown seaweed A. nodosum, a plant biostimulant that contains AA, can also prime plants for defense against pathogen challenges. A previous parallel study comparing the transcriptomes of AA- and ANE-root-treated tomatoes demonstrated significant overlap in transcriptional profiles, a shared induced resistance phenotype, and changes in the accumulation of various defense-related phytohormones. In this work, untargeted metabolomic analysis via liquid chromatography-mass spectrometry was conducted to investigate the local and systemic metabolome-wide remodeling events elicited by AA and ANE root treatment in tomatoes. Our study demonstrated AA and ANE's capacity to locally and systemically alter the metabolome of tomatoes with enrichment of chemical classes and accumulation of metabolites associated with defense-related secondary metabolism. AA- and ANE-root-treated plants showed enrichment of fatty acyl-glycosides and strong modulation of hydroxycinnamic acids and derivatives. Identification of specific metabolites whose accumulation was affected by AA and ANE treatment revealed shared metabolic changes related to ligno-suberin biosynthesis and the synthesis of phenolic compounds. This study highlights the extensive local and systemic metabolic changes in tomatoes induced by treatment with a fatty acid MAMP and a seaweed-derived plant biostimulant with implications for induced resistance and crop improvement.

Mammary Development in Gilts at One Week Postnatal Is Related to Plasma Lysine Concentration at 24 h after Birth, but Not Colostrum Dose.

Perinatal nutrition affects future milk production. The number of mammary epithelial cells affect milk production capacity. Therefore, it was hypothesized that the level of colostrum intake affects the proliferation rate and the total number of mammary epithelial cells in the gland. The ratio of newly synthesized protein to newly synthesized DNA reflects the relative amount of cellular differentiation to cell division. The study objective was to determine the relationship between the level of colostrum intake and 24 h-level of circulating amino acid, glucose and insulin with mammary parenchyma histological features, cell division and protein synthesis over the first week postnatal. One of two standardized doses of a homogenate colostrum sample, 10% (n = 8) and 20% (n = 8) of birth bodyweight, was fed to gilts over the first 24 h postnatal. Gilts were administered deuterium oxide immediately after birth and daily to label newly synthesized DNA and proteins. Gilts were euthanized on postnatal day seven, and DNA and protein were isolated from mammary parenchyma. DNA and protein fractional synthesis (f) and fractional synthetic rate (FSR) were calculated using mass isotopomer distribution analysis. The ratio of protein f and FSR to DNA f and FSR were calculated and used to indicate the relative amounts of differentiation to cell division. Mammary morphological development was also analyzed by measuring the parenchymal epithelial area and the stromal and epithelial proliferation index on postnatal day seven. Colostrum dose was not related to any of the variables used to evaluate mammary development. However, plasma lysine levels at 24 h postnatal were positively related to average daily gain (ADG; r = 0.54, p = 0.05), DNA f (r = 0.57; p = 0.03) and DNA FSR (r = 0.57; p = 0.03) in mammary parenchyma. Plasma lysine was inversely related to the ratio of protein to DNA f and FSR (r = -0.56; p = 0.04). ADG was related to the parenchymal epithelial area and DNA and protein f and FSR (p < 0.05). These relationships support the idea that the nutritional environment affects early mammary development and that higher lysine levels in the perinatal period favored a greater degree of cell division versus differentiation in mammary of neonatal pigs and thus, warrant further investigations.

Bayesian-Weighted Triplet and Quartet Methods for Species Tree Inference.

Inference of the evolutionary histories of species, commonly represented by a species tree, is complicated by the divergent evolutionary history of different parts of the genome. Different loci on the genome can have different histories from the underlying species tree (and each other) due to processes such as incomplete lineage sorting (ILS), gene duplication and loss, and horizontal gene transfer. The multispecies coalescent is a commonly used model for performing inference on species and gene trees in the presence of ILS. This paper introduces Lily-T and Lily-Q, two new methods for species tree inference under the multispecies coalescent. We then compare them to two frequently used methods, SVDQuartets and ASTRAL, using simulated and empirical data. Both methods generally showed improvement over SVDQuartets, and Lily-Q was superior to Lily-T for most simulation settings. The comparison to ASTRAL was more mixed-Lily-Q tended to be better than ASTRAL when the length of recombination-free loci was short, when the coalescent population parameter [Formula: see text] was small, or when the internal branch lengths were longer.

Effects of serine palmitoyltransferase inhibition by myriocin in ad libitum-fed and nutrient-restricted ewes.

The fungal isolate myriocin inhibits serine palmitoyltransferase and de novo ceramide synthesis in rodents; however, the effects of myriocin on ceramide concentrations and metabolism have not been previously investigated in ruminants. In our study, 12 non-lactating crossbred ewes received an intravenous bolus of myriocin (0, 0.1, 0.3, or 1.0 mg/kg/body weight [BW]; CON, LOW, MOD, or HIGH) every 48 h for 17 d. Ewes consumed a high-energy diet from day 1 to 14 and were nutrient-restricted (straw only) from day 15 to 17. Blood was collected preprandial and at 1, 6, and 12 h relative to bolus and nutrient restriction. Tissues were collected following euthanasia on day 17. Plasma was analyzed for free fatty acids (FFAs), glucose, and insulin. Plasma and tissue ceramides were quantified using mass spectrometry. HIGH selectively decreased metabolizable energy intake, BW, and plasma insulin, and increased plasma FFA (Dose, P < 0.05). Myriocin linearly decreased plasma very-long-chain (VLC) ceramide and dihydroceramide (DHCer) by day 13 (Linear, P < 0.05). During nutrient restriction, fold-change in FFA was lower with increasing dose (P < 0.05). Nutrient restriction increased plasma C16:0-Cer, an effect suppressed by MOD and HIGH (Dose × Time, P < 0.05). Myriocin linearly decreased most ceramide and DHCer species in the liver and omental and mesenteric adipose, VLC ceramide and DHCer in the pancreas, and C18:0-Cer in skeletal muscle and subcutaneous adipose tissue (Linear, P ≤ 0.05). We conclude that the intravenous delivery of 0.3 mg of myriocin/kg of BW/48 h decreases circulating and tissue ceramide without modifying energy intake in ruminants.

The Effect of Orally Dosed Levagen+™ (palmitoylethanolamide) on Exercise Recovery in Healthy Males-A Double-Blind, Randomized, Placebo-Controlled Study.

The aim of this study was to evaluate the effect of palmitoylethanolamide (PEA), a cannabimimetic compound and lipid messenger, on recovery from muscle damaging exercise. Twenty-eight healthy young male participants attended the laboratory four times on subsequent days. In the first visit, baseline characteristics were recorded before participants were randomized to consume either liquid PEA (167.5 mg Levagen+ with 832.5 mg maltodextrin) or a matched placebo (1 g maltodextrin) drink. Leg press exercise consisted of four sets at 80% of one repetition maximum followed by a performance set. Muscle soreness, thigh circumference, blood lactate concentration, biomarkers of muscle damage and inflammation, and transcription factor pathways were measured pre- and immediately post-exercise and again at 1, 2, 3, 24, 48, and 72 h post-exercise. The leg press exercise increased (p < 0.05) blood lactate concentration and induced muscle damage as evidenced by increased muscle soreness, thigh circumference, biomarkers of muscle damage, and concentrations of tumor necrosis factor-α. PEA reduced (p < 0.05) myoglobin and blood lactate concentrations and increased protein kinase B phosphorylation following exercise. Taken together, these results indicate PEA supplementation may aid in muscle recovery from repeat bouts of exercise performed within a short duration by reducing myoglobin and lactate concentration.

Gel-seq: A Method for Simultaneous Sequencing Library Preparation of DNA and RNA Using Hydrogel Matrices.

The ability to amplify and sequence either DNA or RNA from small starting samples has only been achieved in the last five years. Unfortunately, the standard protocols for generating genomic or transcriptomic libraries are incompatible and researchers must choose whether to sequence DNA or RNA for a particular sample. Gel-seq solves this problem by enabling researchers to simultaneously prepare libraries for both DNA and RNA starting with 100 - 1000 cells using a simple hydrogel device. This paper presents a detailed approach for the fabrication of the device as well as the biological protocol to generate paired libraries. We designed Gel-seq so that it could be easily implemented by other researchers; many genetics labs already have the necessary equipment to reproduce the Gel-seq device fabrication. Our protocol employs commonly-used kits for both whole-transcript amplification (WTA) and library preparation, which are also likely to be familiar to researchers already versed in generating genomic and transcriptomic libraries. Our approach allows researchers to bring to bear the power of both DNA and RNA sequencing on a single sample without splitting and with negligible added cost.

Gel-seq: whole-genome and transcriptome sequencing by simultaneous low-input DNA and RNA library preparation using semi-permeable hydrogel barriers.

The advent of next generation sequencing has fundamentally changed genomics research. Unfortunately, standard protocols for sequencing the genome and the transcriptome are incompatible. This forces researchers to choose between examining either the DNA or the RNA for a particular sample. Here we describe a new device and method, collectively dubbed Gel-seq, that enables researchers to simultaneously sequence both DNA and RNA from the same sample. This technology makes it possible to directly examine the ways that changes in the genome impact the transcriptome in as few as 100 cells. The heart of the Gel-seq protocol is the physical separation of DNA from RNA. This separation is achieved electrophoretically using a newly designed device that contains several different polyacrylamide membranes. Here we report on the development and validation of this device. We present both the manufacturing protocol for the device and the biological protocol for preparing genetic libraries. Using cell lines with uniform expression (PC3 and Hela), we show that the libraries generated with Gel-seq are similar to those developed using standard methods for either RNA or DNA. Furthermore, we demonstrate the power of Gel-seq by generating a matched genome and transcriptome library from a sample of 100 cells collected from a mouse liver tumor.

An Isolated Traumatic Medial Third Clavicular Fracture Requiring Surgical Fixation.

Fractures of the medial clavicle are rare injuries but are associated with significant morbidity and mortality. The current trend is shifting from conservative treatment to surgical intervention to reduce long-term sequelae. We present an isolated medial clavicular fracture associated with significant displacement and demonstrate excellent results after open reduction and internal fixation.

The development of a short route to the API ropinirole hydrochloride.

A four-step, three-stage synthesis of the API ropinirole hydrochloride has been developed from a commercially available naphthalene derivative. The new route has half the step-count and twice the overall yield of the current manufacturing process. Key features of the synthesis are a regioselective Birch reduction and an ozonolysis with concomitant ring closure to induce the required ring contraction.

Efficacy of cabazitaxel in mouse models of pediatric brain tumors.

BACKGROUND: There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. METHODS: The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. RESULTS: This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. CONCLUSION: These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors.

Bone Osteolysis Following Acromioclavicular Joint Reconstruction Using Synthetic Ligament (Surgilig™).

Good short term results have led to increased use of synthetic ligaments for acute and chronic acromioclavicular joint (ACJ) disruption. They have proved quite safe in the short term but we present two cases of osteolysis following ACJ reconstruction using a synthetic ligament, reminding surgeons of potential complications with artificial ligaments. A high index of suspicion is needed to diagnose such complications early before irretrievable bone loss to osteolysis.

Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells.

Genome sequencing of single cells has a variety of applications, including characterizing difficult-to-culture microorganisms and identifying somatic mutations in single cells from mammalian tissues. A major hurdle in this process is the bias in amplifying the genetic material from a single cell, a procedure known as polymerase cloning. Here we describe the microwell displacement amplification system (MIDAS), a massively parallel polymerase cloning method in which single cells are randomly distributed into hundreds to thousands of nanoliter wells and their genetic material is simultaneously amplified for shotgun sequencing. MIDAS reduces amplification bias because polymerase cloning occurs in physically separated, nanoliter-scale reactors, facilitating the de novo assembly of near-complete microbial genomes from single Escherichia coli cells. In addition, MIDAS allowed us to detect single-copy number changes in primary human adult neurons at 1- to 2-Mb resolution. MIDAS can potentially further the characterization of genomic diversity in many heterogeneous cell populations.

Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model.

The Sonic Hedgehog (Shh) pathway drives a subset of medulloblastomas, a malignant neuroectodermal brain cancer, and other cancers. Small-molecule Shh pathway inhibitors have induced tumor regression in mice and patients with medulloblastoma; however, drug resistance rapidly emerges, in some cases via de novo mutation of the drug target. Here we assess the response and resistance mechanisms to the natural product derivative saridegib in an aggressive Shh-driven mouse medulloblastoma model. In this model, saridegib treatment induced tumor reduction and significantly prolonged survival. Furthermore, the effect of saridegib on tumor-initiating capacity was demonstrated by reduced tumor incidence, slower growth, and spontaneous tumor regression that occurred in allografts generated from previously treated autochthonous medulloblastomas compared with those from untreated donors. Saridegib, a known P-glycoprotein (Pgp) substrate, induced Pgp activity in treated tumors, which likely contributed to emergence of drug resistance. Unlike other Smoothened (Smo) inhibitors, the drug resistance was neither mutation-dependent nor Gli2 amplification-dependent, and saridegib was found to be active in cells with the D473H point mutation that rendered them resistant to another Smo inhibitor, GDC-0449. The fivefold increase in lifespan in mice treated with saridegib as a single agent compares favorably with both targeted and cytotoxic therapies. The absence of genetic mutations that confer resistance distinguishes saridegib from other Smo inhibitors.

Experimental microsphere targeting in a representative hepatic artery system.

Recent work employing the computational fluid-particle modeling of the hepatic arteries has identified a correlation between particle release position and downstream branch distribution for direct tumor-targeting in radioembolization procedures. An experimental model has been constructed to evaluate the underlying simulation theory and determine its feasibility for future clinical use. A scaled model of a generalized hepatic system with a single inlet and five outlet branches was fabricated to replicate the fluid dynamics in the hepatic arteries of diseased livers. Assuming steady flow, neutrally buoyant microspheres were released from controlled locations within the inlet of the model and the resulting output distributions were recorded. Fluid and particle transport simulations were conducted with identical parameters. The resulting experimentally and simulation-derived microsphere distributions were compared. The experimental microsphere distribution exhibited a clear dependence on injection location that correlated very strongly with the computationally predicted results. Individual branch targeting was possible for each of the five outputs. The experimental results validate the simulation methodology for achieving targeted microsphere distributions in a known geometry under constant flow conditions.

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults--the Clavicle Trial: study protocol for a multicentre randomized controlled trial.

BACKGROUND: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision. METHODS/DESIGN: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively. DISCUSSION: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity. TRIAL REGISTRATION: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007.