Colostrum insulin supplementation to neonatal Holstein bulls affects small intestinal histomorphology, mRNA expression, and enzymatic activity with minor influences on peripheral metabolism.

The objectives of this study were to evaluate how varying colostral insulin concentrations influenced small intestinal development and peripheral metabolism in neonatal Holstein bulls. Insulin was supplemented to approximately 5× (70.0 µg/L; n = 16) or 10× (149.7 µg/L; n = 16) the basal colostrum insulin (12.9 µg/L; BI, n = 16) concentration to maintain equivalent macronutrient intake (crude fat: 4.1 ± 0.06%; crude protein: 11.7 ± 0.05%; and lactose: 1.9 ± 0.01%) among treatments. Colostrum was fed at 2, 14, and 26 h postnatal and blood metabolites and insulin concentration were measured at 0, 30, 60, 90, 120, 180, 240, 360, 480, and 600 min postprandial respective to the first and second colostrum meal. At 30 h postnatal, a subset of calves (n = 8/treatment) were killed to excise the gastrointestinal and visceral tissues. Gastrointestinal and visceral gross morphology and dry matter and small intestinal histomorphology, gene expression, and carbohydrase activity were assessed. Insulin supplementation tended to linearly reduce the glucose clearance rate following the first meal, whereas after the second meal, supplementation linearly increased the rate of glucose absorption and nonesterified fatty acid clearance rate, decreased the time to maximum glucose concentrations, and decreased the time to reach minimum nonesterified fatty acid concentrations. Additionally, insulin clearance rate was linearly increased by insulin supplementation following the second colostrum feeding. However, there were no overall differences between treatments in the concentrations of glucose, nonesterified fatty acids, or insulin in plasma or serum. With respect to macroscopic intestinal development, dry rumen tissue mass linearly decreased when insulin was supplemented in colostrum, and supplementation linearly increased duodenal dry tissue density (g dry matter/cm) while tending to increase duodenal dry tissue weight. Increasing the colostrum insulin concentration improved small intestinal histomorphological development in the distal small intestine, as ileal villi height and mucosal-serosal surface area index were increased by supplementing insulin. Lactase enzymatic activity linearly increased in the proximal jejunum while ileal isomaltase activity linearly decreased with insulin supplementation. These data indicate that changes in colostrum insulin concentrations rapidly affect gastrointestinal growth prioritization and carbohydrase activity. The changes in gastrointestinal ontology result in minor changes in postprandial metabolite availability and clearance.

Research needs, environmental concerns, and logistical considerations for incorporating livestock grazing into coastal upland habitat management.

Along the Gulf of Mexico (GoM) coast, natural resource managers continually struggle with managing coastal uplands due to front-end costs, prolonged maintenance, and habitat-specific ecological needs. Prescribed fire, mechanical removal, and chemical treatments are common habitat management techniques used to remove invasive species, clear understory, and achieve other management goals. However, rapid development and changing climate exacerbate the difficulty in using these techniques. A potential alternative or complementary technique is using livestock for habitat management (i.e., targeted or controlled grazing). In other regions of the world, using livestock for conservation or restoration of managed lands has shown to be a less intrusive and more financially viable alternative. To better understand the research needs, logistical, and environmental concerns related to using livestock for habitat management in the coastal uplands of the GoM, we developed and distributed a survey to three groups of land users, including natural resource managers, researchers, and livestock producers in the region. Survey results show that over 96% of respondents are interested in using livestock for habitat management, but less than 10% of respondents were aware of any information that could be used to inform grazing practices for coastal upland habitat management along the Gulf of Mexico coast. There were differences among surveyed groups, but generally small-sized cattle breeds and goats were identified as the livestock with the most potential for environmental benefit and ease of containment. General concerns and areas for further investigation were implementation (e.g., which livestock type to use and grazing intensity), logistical considerations (e.g., fencing and rotational frequency), impacts of grazing on water quality, wildlife, vegetation, and livestock nutrition. Survey respondents overwhelmingly (at least 75% of each group) indicated that livestock grazing ideally would not be a standalone management practice and should be used in conjunction with other habitat management techniques such as prescribed burns, mechanical clearing, or chemical treatments. The results of the survey could be used to develop applied research projects and guidance documents that directly address informational needs related to using livestock for habitat management of coastal uplands along the Gulf of Mexico coast.

Geographically diverse canid sampling provides novel insights into pre-industrial microbiomes.

Canine microbiome studies are often limited in the geographic and temporal scope of samples studied. This results in a paucity of data on the canine microbiome around the world, especially in contexts where dogs may not be pets or human associated. Here, we present the shotgun sequences of fecal microbiomes of pet dogs from South Africa, shelter and stray dogs from India, and stray village dogs in Laos. We additionally performed a dietary experiment with dogs housed in a veterinary medical school, attempting to replicate the diet of the sampled dogs from Laos. We analyse the taxonomic diversity in these populations and identify the underlying functional redundancy of these microbiomes. Our results show that diet alone is not sufficient to recapitulate the higher diversity seen in the microbiome of dogs from Laos. Comparisons to previous studies and ancient dog fecal microbiomes highlight the need for greater population diversity in studies of canine microbiomes, as modern analogues can provide better comparisons to ancient microbiomes. We identify trends in microbial diversity and industrialization in dogs that mirror results of human studies, suggesting future research can make use of these companion animals as substitutes for humans in studying the effects of industrialization on the microbiome.

Multistage coupling of independent laser-plasma accelerators.

Laser-plasma accelerators (LPAs) are capable of accelerating charged particles to very high energies in very compact structures. In theory, therefore, they offer advantages over conventional, large-scale particle accelerators. However, the energy gain in a single-stage LPA can be limited by laser diffraction, dephasing, electron-beam loading and laser-energy depletion. The problem of laser diffraction can be addressed by using laser-pulse guiding and preformed plasma waveguides to maintain the required laser intensity over distances of many Rayleigh lengths; dephasing can be mitigated by longitudinal tailoring of the plasma density; and beam loading can be controlled by proper shaping of the electron beam. To increase the beam energy further, it is necessary to tackle the problem of the depletion of laser energy, by sequencing the accelerator into stages, each powered by a separate laser pulse. Here, we present results from an experiment that demonstrates such staging. Two LPA stages were coupled over a short distance (as is needed to preserve the average acceleration gradient) by a plasma mirror. Stable electron beams from a first LPA were focused to a twenty-micrometre radius--by a discharge capillary-based active plasma lens--into a second LPA, such that the beams interacted with the wakefield excited by a separate laser. Staged acceleration by the wakefield of the second stage is detected via an energy gain of 100 megaelectronvolts for a subset of the electron beam. Changing the arrival time of the electron beam with respect to the second-stage laser pulse allowed us to reconstruct the temporal wakefield structure and to determine the plasma density. Our results indicate that the fundamental limitation to energy gain presented by laser depletion can be overcome by using staged acceleration, suggesting a way of reaching the electron energies required for collider applications.

Feeding high amounts of almond hulls to lactating cows.

California is the leading state for the production of almonds, with more than 400,000 bearing hectares of orchards that produced approximately 1 billion kilograms of shelled nuts in 2017. Almond hulls (AH) are a regional by-product feedstuff fed predominantly to dairy cattle in California. A 2012 study surveyed 40 dairy farms in California and found that 39 out of 104 total mixed rations contained AH, with a mean daily feeding rate of 1.45 kg/cow. In 2017, approximately 2 billion kilograms of AH was produced. At a feeding rate of 1.45 kg/cow daily, even if all 1.7 million lactating cows in California are consuming AH, there will be a surplus of AH on the market as the approximately 130,000 nonbearing hectares come into nut production. Therefore, the potential of feeding varying amounts of AH to lactating dairy cows was investigated using 12 Holstein cows with 4 primiparous and 8 multiparous cows. The dietary treatments were 4 total mixed rations containing 0, 7, 13, or 20% AH. The AH used contained 12.8% crude fiber (as-is basis), which was below the 15% legal limit set by state feed regulations. Diets were formulated so that as the inclusion rate of AH increased, the amount of steam-flaked corn and soyhull pellets decreased and soybean meal inclusion increased. Experimental design was a replicated 4 × 4 Latin square. Diet had a cubic effect on actual milk yield, energy-corrected milk yield, and dry matter intake, with the 7% AH diet having the highest values and the 13% AH diet having the lowest. The percent and yield of total solids and the yields of lactose and fat did not differ with diet, but percent and yield of protein declined linearly with increased AH inclusion, and fat percent increased linearly. Apparent total-tract digestibilities of dry matter and organic matter were higher with the inclusion of AH in the diet. Total percentage of the day spent ruminating increased linearly with higher amounts of AH. Overall, this work demonstrated that AH can be fed at varying amounts, up to 20% of the diet, to lactating dairy cows to support high levels of milk production and that increasing amounts of AH (up to 20%) in the diet could lead to improved digestibility and milk fat percentage but decreased milk protein production.

Petawatt Laser Guiding and Electron Beam Acceleration to 8 GeV in a Laser-Heated Capillary Discharge Waveguide.

Guiding of relativistically intense laser pulses with peak power of 0.85 PW over 15 diffraction lengths was demonstrated by increasing the focusing strength of a capillary discharge waveguide using laser inverse bremsstrahlung heating. This allowed for the production of electron beams with quasimonoenergetic peaks up to 7.8 GeV, double the energy that was previously demonstrated. Charge was 5 pC at 7.8 GeV and up to 62 pC in 6 GeV peaks, and typical beam divergence was 0.2 mrad.

Measured Emittance Dependence on the Injection Method in Laser Plasma Accelerators.

Single-shot, charge-dependent emittance measurements of electron beams generated by a laser plasma accelerator (LPA) reveal that shock-induced density down-ramp injection produces beams with normalized emittances a factor of 2 smaller than beams produced via ionization injection. Such a comparison is made possible by the tunable LPA setup, which allows electron beams with nearly identical central energy and peak spectral charge density to be produced using the two distinct injection mechanisms. Parametric measurements of this type are essential for the development of LPA-based applications which ultimately require high charge density and low emittance.

Effects of realimentation after nutrient restriction during mid- to late gestation on pancreatic digestive enzymes, serum insulin and glucose levels, and insulin-containing cell cluster morphology.

This study examined effects of stage of gestation and nutrient restriction with subsequent realimentation on maternal and foetal bovine pancreatic function. Dietary treatments were assigned on day 30 of pregnancy and included: control (CON; 100% requirements; n = 18) and restricted (R; 60% requirements; n = 30). On day 85, cows were slaughtered (CON, n = 6; R, n = 6), remained on control (CC; n = 12) and restricted (RR; n = 12), or realimented to control (RC; n = 11). On day 140, cows were slaughtered (CC, n = 6; RR, n = 6; RC, n = 5), remained on control (CCC, n = 6; RCC, n = 5) or realimented to control (RRC, n = 6). On day 254, the remaining cows were slaughtered and serum samples were collected from the maternal jugular vein and umbilical cord to determine insulin and glucose concentrations. Pancreases from cows and foetuses were removed, weighed, and subsampled for enzyme and histological analysis. As gestation progressed, maternal pancreatic α-amylase activity decreased and serum insulin concentrations increased (p ≤ 0.03). Foetal pancreatic trypsin activity increased (p < 0.001) with advancing gestation. Foetal pancreases subjected to realimentation (CCC vs. RCC and RRC) had increased protein and α-amylase activity at day 254 (p ≤ 0.02), while trypsin (U/g protein; p = 0.02) demonstrated the opposite effect. No treatment effects were observed for maternal or foetal pancreatic insulin-containing cell clusters. Foetal serum insulin and glucose levels were reduced with advancing gestation (p ≤ 0.03). The largest maternal insulin-containing cell cluster was not influenced by advancing gestation, while foetal clusters grew throughout (p = 0.01). These effects indicate that maternal digestive enzymes are influenced by nutrient restriction and there is a potential for programming of increased foetal digestive enzyme production resulting from previous maternal nutrient restriction.

Cell survival signaling in the bovine mammary gland during the transition from lactation to involution.

In dairy cows, mammary gland involution, and thus a decline in milk production, occurs following peak lactation. To examine the cell signaling pathways regulating involution of the mammary gland, signal transducer and activator of transcription factors (STAT5 and 3), suppressors of cytokine signaling (SOCS1-3 and CIS), insulin-like growth factors (IGF1 and 2), and protein kinase B (Akt) were examined. Mammary involution was induced by termination of milking, and alveolar tissue was collected from 52 nonpregnant, primiparous, mid-lactation Holstein-Friesian cows killed at 0, 6, 12, 18, 24, 36, 72, and 192h postmilking. Qualitative immunohistochemistry showed that activated (phosphorylated) STAT5-P was localized in nuclei of mammary epithelial cells at the early time points, with detection levels decreasing by 24h postmilking. In contrast, STAT3-P was barely detectable at the early time points, with detection levels increasing following longer postmilking periods. This was supported by Western analysis, which showed a decline in STAT5 and STAT5-P protein levels by 24h postmilking, no change in STAT3 levels, and an increase in STAT3-P protein (barely detectable at the early time points) by 72h postmilking. Quantitative real-time reverse transcription PCR analysis showed SOCS1 and SOCS3 mRNA increased by 72h postmilking compared with 6h postmilking. The SOCS2 mRNA remained unchanged across the time series, whereas CIS decreased by 18h postmilking and remained lower compared with that at 6h postmilking until 72h postmilking. The IGF1 mRNA increased by 192h postmilking, whereas IGF2 mRNA decreased by 18h postmilking compared with 6h postmilking. The IGFBP5 mRNA and protein levels of Akt and Akt-P remained unchanged over the time series. These results show that reciprocal activation of STAT5 and STAT3 occurs at the onset of mammary gland involution in the bovine, albeit at a slower rate than in rodents. Mathematical modeling of the pathways indicated that activated STAT3 could block the STAT5 pathway by upregulating SOCS3. The regulation of IGF1-Akt signaling suggests that by 192h postmilking in dairy cows, the involution process is still in the reversible phase, with quiescent mammary epithelial cells not yet in the senescent phase.

Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma.

BACKGROUND: Patients with recurrent glioblastoma have a poor outcome. Data from the phase III registration trial comparing tumour-treating alternating electric fields (TTFields) vs chemotherapy provided a unique opportunity to study dexamethasone effects on patient outcome unencumbered by the confounding immune and myeloablative side effects of chemotherapy. METHODS: Using an unsupervised binary partitioning algorithm, we segregated both cohorts of the trial based on the dexamethasone dose that yielded the greatest statistical difference in overall survival (OS). The results were validated in a separate cohort treated in a single institution with TTFields and their T lymphocytes were correlated with OS. RESULTS: Patients who used dexamethasone doses >4.1 mg per day had a significant reduction in OS when compared with those who used ⩽4.1 mg per day, 4.8 vs 11.0 months respectively (χ(2)=34.6, P<0.0001) in the TTField-treated cohort and 6.0 vs 8.9 months respectively (χ(2)=10.0, P<0.0015) in the chemotherapy-treated cohort. In a single institution validation cohort treated with TTFields, the median OS of patients who used dexamethasone >4.1 mg per day was 3.2 months compared with those who used ⩽4.1 mg per day was 8.7 months (χ(2)=11.1, P=0.0009). There was a significant correlation between OS and T-lymphocyte counts. CONCLUSIONS: Dexamethasone exerted profound effects on both TTFields and chemotherapy efficacy resulting in lower patient OS. Therefore, global immunosuppression by dexamethasone likely interferes with immune functions that are necessary for the treatment of glioblastoma.

The effect of milking reinitiation following extended nonmilking periods on lactation in primiparous dairy cows.

In dairy cows, extended periods of nonmilking results in reduced milk secretion, modifications in milk composition, and eventually involution of the mammary glands. The aim of this study was to determine the effect of extended nonmilking periods on the recovery of milk yield and composition, and levels of prolactin and insulin-like growth factor-I in pasture-fed cows after resuming milking. Pasture-fed, primiparous, nonpregnant, Friesian dairy cows at mid lactation (mean ± standard deviation, 97 ± 2d in milk, 14.0 ± 2.5 L/d) were divided into 3 groups (n=6 per group). The cows were subjected to nonmilking periods of 7, 14, or 28d. Twice-daily milking was resumed for 7d following the nonmilking periods. Milk yield recoveries at the end of the 7-d remilking period were 91, 51, and 29% for the 7, 14, and 28-d nonmilked groups, respectively. The somatic cell count declined to less than 400,000 cells/mL by d 3 and 6 of remilking for the 7- and 14-d-nonmilked groups, respectively, but remained greater than 800,000 cells/mL in the 28-d-nonmilked group through the 7-d remilking period. By d 7 of remilking, the somatic cell count for the 7-d-nonmilked group was not different from pretrial values. Upon remilking, the milk fat content returned to pretrial values for the 7- and 14-d-nonmilked groups, although it remained lower than pretrial for the 28-d-nonmilked group. All 3 nonmilked groups had a higher milk protein content following 7d of remilking, compared with pretrial values. The lactose content returned to pretrial values for the 7-d-nonmilked group but remained lower for the 14- and 28-d-nonmilked groups. Circulating prolactin concentrations increased once remilking was resumed, compared with the pretrial and nonmilking periods. Prolactin concentrations did not majorly differ between the groups, with the levels upon 7d of remilking remaining higher than the pretrial concentrations and the nonmilked periods. Plasma concentrations of insulin-like growth factor-I increased during the nonmilking period and were greater in all 3 nonmilked groups on d 1 of remilking than pretrial values and returned to pretrial concentrations following remilking for the 7-d-nonmilked group, whereas the 14- and 28-d-nonmilked groups remained higher than the pretrial values. These data indicate that the process of involution is fully reversed after remilking following 7d of milk stasis but more extended periods of nonmilking prevent the complete recovery of lactation. However, even after 28d of milk stasis, the milk synthesis capacity of the mammary gland could still be partially recovered.

Effects of photoperiod on food intake, activity and metabolic rate in adult neutered male cats.

With the continued rise in feline obesity, novel weight management strategies are needed. To date, strategies aimed at altering physical activity, an important factor in weight maintenance, have been lacking. Photoperiod is known to cause physiological changes in seasonal mammals, including changes in body weight (BW) and reproductive status. Thus, our objective was to determine the effect of increased photoperiod (longer days) on voluntary physical activity levels, resting metabolic rate (RMR), food intake required to maintain BW, and fasting serum leptin and ghrelin concentrations in adult cats. Eleven healthy, adult, neutered, male domestic shorthair cats were used in a randomized crossover design study. During two 12-week periods, cats were exposed to either a short-day (SD) photoperiod of 8 h light: 16 h dark or a long-day (LD) photoperiod of 16 h light: 8 h dark. Cats were fed a commercial diet to maintain baseline BW. In addition to daily food intake and twice-weekly BW, RMR (via indirect calorimetry), body composition [via dual-energy X-ray absorptiometry (DEXA)] and physical activity (via Actical activity monitors) were measured at week 0 and 12 of each period. Fasting serum leptin and ghrelin concentrations were measured at week 0, 6 and 12 of each period. Average hourly physical activity was greater (p = 0.008) in LD vs. SD cats (3770 vs. 3129 activity counts/h), which was primarily due to increased (p < 0.001) dark period activity (1188 vs. 710 activity counts/h). This corresponded to higher (p < 0.0001) daily metabolizable energy intake (mean over 12-week period: 196 vs. 187 kcal/day), and increased (p = 0.048) RMR in LD cats (9.02 vs. 8.37 kcal/h). Body composition, serum leptin and serum ghrelin were not altered by photoperiod. More research is needed to determine potential mechanisms by which these physiological changes occurred and how they may apply to weight management strategies.

Effects of nutrient restriction and melatonin supplementation on maternal and foetal hepatic and small intestinal energy utilization.

To determine how nutrient restriction and melatonin supplementation influence ewe and foetal hepatic and small intestinal energy use, 32 primiparous ewes on d 50 of gestation were fed 60% (RES) or 100% (ADQ) of NRC recommendations with 0 (CON) or 5 mg/d (MEL) of dietary melatonin. On d 130 of gestation, small intestine and liver were weighed and collected. Data were analysed as a completely randomized design with a 2 × 2 factorial arrangement of treatments. Liver weight (g/kg EBW) decreased (p = 0.02) in RES ewes. Jejunum weight (g/kg BW) increased (interaction p = 0.04) in ADQ-MEL ewes compared with all other treatments. Total in vitro O2 consumption (mol/min/tissue) and total citrate synthase activity (mol/min/tissue and mol/min/kg EBW) in liver decreased (p ≤ 0.03) in RES ewes. Oxygen consumption (mol/min/kg EBW) increased (interaction p = 0.02) in jejunum of ADQ-CON versus RES-MEL and ADQ-CON. Citrate synthase activity (mol/min/kg of EBW) increased (interaction p = 0.03) in jejunum of ADQ-MEL compared with RES-MEL and ADQ-CON. Foetal liver weight (g/kg BW) decreased (p = 0.02) in RES versus ADQ. Foetal small intestine weight (g/kg BW) decreased (interaction p = 0.05) in RES-MEL versus ADQ-MEL. Total O2 consumption (mol/min/tissue) and total citrate synthase activity (mol/min/kg of BW) in foetal liver decreased (p ≤ 0.05) in RES versus ADQ. Foetal small intestinal O2 consumption (mol/min/kg of BW) was greater (interaction p = 0.03) in RES-CON and ADQ-MEL than RES-MEL and ADQ-CON. Maternal nutrient restriction had a greater effect than melatonin supplementation on liver and jejunum mass and energy utilization in dams and foetuses. Because intestinal mass and energy utilization were more responsive to melatonin supplementation in ewes fed adequate nutrition compared with restricted ewes, melatonin may have limited use as a therapeutic supplement to help overcome potential negative effects of nutrient restriction.

An experimental platform for investigation of the Zeeman effect in strong magnetic fields.

An experimental platform is developed for the investigation of the Zeeman effect in strong magnetic fields. Mega-Gauss magnetic fields are generated by a 1 MA Zebra pulsed power machine using metal rod loads. A gas jet or CH oil on the load is the source of hydrogen. Excited hydrogen atoms are backlit by black body radiation from the rod load. Hydrogen absorption spectra are recorded with a grating spectrometer and intensified gated CCD camera. The experimental platform enables the observation of the quadratic Zeeman effect in hydrogen gas jets using the spectral shift of the central line in the Zeeman triplet. Other gases can be studied using the gas jet method.

High repetition-rate dual-channel X-ray spectrometer for high-intensity laser-plasma experiments.

We describe the development and demonstration of a high-repetition-rate-capable dual-channel (DC) x-ray spectrometer designed for high-intensity laser-plasma experiments (≥1×1021 W/cm2). The spectrometer, which operates at high repetition rates, is limited only by the refresh rate of targets and the camera's frame rate. It features two channels, each equipped with a flat highly oriented pyrolytic graphite (HOPG) crystal and a unique detector plane, allowing it to resolve two distinct x-ray bands: approximately 7-10 and 10-13 keV. Each detector plate carrier holds two slots for active (scintillators) or passive (imaging plates) x-ray detectors. We present the design and testing of the HR-DC-HOPG using both the COMET laser (10 J, 0.5 ps shot/4 min) at LLNL's Jupiter Laser Facility and the SCARLET laser (10 J, 30 fs shot/min) at Ohio State University. The results demonstrate the spectrometer's performance across various laser energies, target materials, pulse shapes, and detector types.

Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function.

Timing and duration of nutrient restriction and its impacts on placental development and umbilical blood flow in adolescent sheep.

We hypothesized that nutrient restriction from day 50-90 of gestation decreases umbilical blood flow and that umbilical blood flow would recover to control values upon realimentation during late gestation (d 90 to 130) or remain reduced in ewes that continued to be nutrient restricted. On d 50 of gestation, young nulliparous whiteface ewes (6-8 mo; n = 41) carrying singletons were randomly assigned to two dietary treatments: 100% of NRC recommendations (CON) or 60% of CON (RES). On d 90 of gestation, ewes either remained on CON or RES until d 130, or CON ewes were RES from d 90 to 130, or RES ewes were realimented to CON from d 90 to 130. This resulted in 4 treatment groups on day 130: CON-CON, CON-RES, RES-RES, RES-CON. Umbilical blood flow and fetal and placental measurements were obtained via ultrasonography every 10 days from day 50-110. Non-survival surgeries were performed on days 50, 90, and 130 (n = 6-7 ewes/group) where uterine artery and umbilical blood flows were measured during surgery via ultrasonography. Conceptus weights were recorded and placentomes collected to determine binucleate cell numbers. The study was conducted as a completely randomized design arrangement with repeated measures. Data were analyzed using the MIXED procedure of SAS. There was a nutritional treatment by day interaction (P < 0.01) with CON ewes having greater umbilical blood flow compared with RES by d 90. Fetal biparietal distance, abdominal width, and kidney area increased (P < 0.05) in CON-RES with all these measurements increasing during late gestation. We partially accept our hypothesis as nutrient restriction during mid gestation decreased umbilical blood flow. However, blood flow did not return to control levels upon realimentation. By d 130, fetal and placental weights were similar between RES-RES and CON-CON. Binucleate cell numbers in the fetal trophoblast were not influenced by nutritional treatments. Our findings suggest that refeeding previously nutrient restricted pregnant adolescent ewes to control levels does not reestablish umbilical blood flow. Adequate placental development during mid gestation could protect the fetus from a decreased umbilical blood flow later in gestation when nutrients were limited by 40%.

Flexible tape-drive target system for secondary high-intensity laser-driven sources.

We present the development of a flexible tape-drive target system to generate and control secondary high-intensity laser-plasma sources. Its adjustable design permits the generation of relativistic MeV particles and x rays at high-intensity (i.e., ≥1 × 1018 W cm-2) laser facilities, at high repetition rates (>1 Hz). The compact and robust structure shows good mechanical stability and a high target placement accuracy (<4 µm RMS). Its compact and flexible design allows for mounting in both the horizontal and vertical planes, which makes it practical for use in cluttered laser-plasma experimental setups. The design permits ∼170° of access on the laser-driver side and 120° of diagnostic access at the rear. A range of adapted apertures have been designed and tested to be easily implemented to the targetry system. The design and performance testing of the tape-drive system in the context of two experiments performed at the COMET laser facility at the Lawrence Livermore National Laboratory and at the Advanced Lasers and Extreme Photonics (ALEPH) facility at Colorado State University are discussed. Experimental data showing that the designed prototype is also able to both generate and focus high-intensity laser-driven protons at high repetition rates are also presented.

A flexible proton beam imaging energy spectrometer (PROBIES) for high repetition rate or single-shot high energy density (HED) experiments (invited).

The PROBIES diagnostic is a new, highly flexible, imaging and energy spectrometer designed for laser-accelerated protons. The diagnostic can detect low-mode spatial variations in the proton beam profile while resolving multiple energies on a single detector or more. When a radiochromic film stack is employed for "single-shot mode," the energy resolution of the stack can be greatly increased while reducing the need for large numbers of films; for example, a recently deployed version allowed for 180 unique energy measurements spanning ∼3 to 75 MeV with <0.4 MeV resolution using just 20 films vs 180 for a comparable traditional film and filter stack. When utilized with a scintillator, the diagnostic can be run in high-rep-rate (>Hz rate) mode to recover nine proton energy bins. We also demonstrate a deep learning-based method to analyze data from synthetic PROBIES images with greater than 95% accuracy on sub-millisecond timescales and retrained with experimental data to analyze real-world images on sub-millisecond time-scales with comparable accuracy.

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.